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International audience; Since 2016, the French Society of Hypertension has warned about the decline in the management of high blood pressure in France: stagnation, or even decreased number of people who know their blood pressure level, take a treatment and are controlled. These results are lower than those observed in many other countries. Blood pressure is measured with an old method in the doctor's office. Accepted, simple and cost-effective, this method is currently unavoidable for reasons of feasibility and social habit. It has been used in observational and intervention studies that are the basis of the medical reasoning for screening, treatment and drug control of hypertension. In practice, it is too often poorly applied and unpredictable. It is now necessary to measure blood pressure in mmHg using a validated oscillometric automatic device coupled to a specific upper arm cuff adapted to the arm circumferences for the diagnosis and monitoring of high blood pressure in the doctor's office and at home. The auscultatoric measurement is only recommended if any doubt about the reliability of the electronic measurement. Blood pressure measurement is basically performed on both arms to detect asymmetry and then on the arm with the highest blood pressure. It is performed in sitting or lying position after a few minutes of rest without speaking and without having smoked and then in standing position to diagnose orthostatic hypotension, especially in elderly, diabetic and multi-medicated subjects. The blood pressure measurement during the consultation must be repeated and include at least 3 consecutive measurements at one minute intervals. The average of the last 2 measurements determines the blood pressure level. It is recommended to perform BP measurements outside the medical environment for the diagnosis and monitoring of hypertension; Home BP measurement is preferred to ambulatory blood pressure measurement for practical reasons unless otherwise specified. The home blood pressure measurement should include three measurements in the morning at breakfast and three measurements in the evening before bedtime at one minute intervals for at least three days. Prior training must be provided. In treated hypertensive patients, a masked hypertension should be considered as an uncontrolled hypertension and antihypertensive therapy adapted accordingly. The measurement of central BP pressure (aorta) should be limited to clinical research.

International audience; Background: We hypothesized that dietary sodium may modulate the effect of systolic blood pressure and other nonhemodynamic factors, such as high uric acid and renal dysfunction, on changes in the left ventricular mass after renal transplantation. The objective of the present 3-year follow-up longitudinal study was to assess the concomitant influence of these factors on changes in the left ventricular mass after renal transplantation.Methods: Twenty-four-hour urinary sodium excretion, glomerular filtration rate (isotopic clearance), and left ventricular mass (echocardiography) assessment were done in 165 renal transplant patients during the first year and after a follow-up of 3 years after renal transplantation.Results: At follow-up, therapy of hypertension was associated with normalization of blood pressure in 64% and a decrease in the prevalence of left ventricular hypertrophy from 66% to 56%. At baseline and follow-up, systolic blood pressure, sodium intake, and serum uric acid emerged as independent and significant determinants of the final left ventricular mass index. When the population was divided according to sex-specific tertiles of the final 24-hr urinary sodium excretion, the relationship between change in serum uric acid during follow-up, final left ventricular mass index, and final glomerular filtration rate was significant only on the highest tertile of 24-hr urinary sodium excretion.Conclusion: The decrease in the prevalence of left ventricular hypertrophy after renal transplantation is blunted by high sodium intake. Persistence of the left ventricular hypertrophy may result from the combined adverse influences of excessive dietary sodium intake and increased serum uric acid during follow-up despite pharmacological control of blood pressure.

The DENERHTN trial (Renal Denervation for Hypertension) confirmed the blood pressure (BP) lowering efficacy of renal denervation added to a standardized stepped-care antihypertensive treatment for resistant hypertension at 6 months. We report here the effect of denervation on 24-hour BP and its variability and look for parameters that predicted the BP response. Patients with resistant hypertension were randomly assigned to denervation plus stepped-care treatment or treatment alone (control). Average and standard deviation of 24-hour, daytime, and nighttime BP and the smoothness index were calculated on recordings performed at randomization and 6 months. Responders were defined as a 6-month 24-hour systolic BP reduction ≥20 mm Hg. Analyses were performed on the per-protocol population. The significantly greater BP reduction in the denervation group was associated with a higher smoothness index ( P =0.02). Variability of 24-hour, daytime, and nighttime BP did not change significantly from baseline to 6 months in both groups. The number of responders was greater in the denervation (20/44, 44.5%) than in the control group (11/53, 20.8%; P =0.01). In the discriminant analysis, baseline average nighttime systolic BP and standard deviation were significant predictors of the systolic BP response in the denervation group only, allowing adequate responder classification of 70% of the patients. Our results show that denervation lowers ambulatory BP homogeneously over 24 hours in patients with resistant hypertension and suggest that nighttime systolic BP and variability are predictors of the BP response to denervation. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01570777.

Background: The DENERHTN trial (Renal Denervation for Hypertension) confirmed the blood pressure–lowering efficacy of renal denervation added to a standardized stepped-care antihypertensive treatment for resistant hypertension at 6 months. We report the influence of adherence to antihypertensive treatment on blood pressure control. Methods: One hundred six patients with hypertension resistant to 4 weeks of treatment with indapamide 1.5 mg/d, ramipril 10 mg/d (or irbesartan 300 mg/d), and amlodipine 10 mg/d were randomly assigned to renal denervation plus standardized stepped-care antihypertensive treatment, or the same antihypertensive treatment alone. For standardized stepped-care antihypertensive treatment, spironolactone 25 mg/d, bisoprolol 10 mg/d, prazosin 5 mg/d, and rilmenidine 1 mg/d were sequentially added at monthly visits if home blood pressure was ≥135/85 mm Hg after randomization. We assessed adherence to antihypertensive treatment at 6 months by drug screening in urine/plasma samples from 85 patients. Results: The numbers of fully adherent (20/40 versus 21/45), partially nonadherent (13/40 versus 20/45), or completely nonadherent patients (7/40 versus 4/45) to antihypertensive treatment were not different in the renal denervation and the control groups, respectively ( P =0.3605). The difference in the change in daytime ambulatory systolic blood pressure from baseline to 6 months between the 2 groups was –6.7 mm Hg ( P =0.0461) in fully adherent and –7.8 mm Hg ( P =0.0996) in nonadherent (partially nonadherent plus completely nonadherent) patients. The between-patient variability of daytime ambulatory systolic blood pressure was greater for nonadherent than for fully adherent patients. Conclusions: In the DENERHTN trial, the prevalence of nonadherence to antihypertensive drugs at 6 months was high (≈50%) but not different in the renal denervation and control groups. Regardless of adherence to treatment, renal denervation plus standardized stepped-care antihypertensive treatment resulted in a greater decrease in blood pressure than standardized stepped-care antihypertensive treatment alone. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01570777.

BackgroundCardiovascular mortality is increased in patients with rheumatoid arthritis (RA). RA is associated with an increased left ventricular mass index (LVMI), a strong marker of cardiovascular mortality, and vessel abnormalities. Experimental studies have suggested that tumour necrosis factor α (TNFα) may induce LV hypertrophy.ObjectiveTo study the effect of medium-term (3- and 6-months) treatment with the TNFα inhibitor etanercept (ETN) and synthetic disease-modifying antirheumatic drugs (sDMARDs) on LV morphological features and arterial stiffness in patients with RA.MethodsConsecutive female patients with active RA requiring treatment with ETN (n=28) or sDMARDs (n=20) were included. Clinical and biological monitoring, echocardiography and pulse wave velocity (PWV) assessment were performed at inclusion and at 3 and 6 months after the start of treatment. Paired t tests and multivariate linear regression analysis were used.ResultsMean LVMI tended to be higher at baseline in the ETN group than in the sDMARD group (96.5±19.8 vs 84.3±26.8 g/m2; p=0.11 for the ETN and sDMARD groups, respectively). In patients with ETN treatment, mean LVMI was significantly decreased at 3 and 6 months (−6.3±7.6 and −14.2±9.3 g/m2; p2, respectively). Blood pressure (BP) and aortic PWV were not changed by either treatment.ConclusionsETN induced a significant decrease in LVMI with medium-term treatment with no change in BP or PWV. TNFα may be an important factor of LV hypertrophy, which may explain the benefit of TNF inhibitors on cardiovascular morbidity and mortality in RA. These results need to be confirmed by larger studies and with other TNF inhibitors.

Summary Objective L-Thyroxine-suppressive therapy benefits high-risk differentiated thyroid cancer patients by decreasing recurrence rates and cancer-related mortality. However, fully suppressed serum thyroid-stimulating hormone (TSH) implies a state of subclinical hyperthyroidism (SCH) with associated adverse cardiac effects. Because left ventricular (LV) diastolic dysfunction may be the first manifestation of more severe LV failure, and to balance the risks from thyroid cancer recurrence with risks of cardiac failure, the purpose of this study was to analyse new parameters of LV function in asymptomatic patients with exogenous SCH. Design Case–control study with 24 patients on TSH-suppressive therapy of short duration (≤4 years) after thyroid ablative therapy for differentiated thyroid carcinoma and 20 age- and sex-matched subjects. Measurements LV function [LV global strain and strain rate (SR) curves] was assessed by speckle tracking imaging echocardiography in each subject. Results Patients and controls do not differ in body mass index, systolic blood pressure and heart rate. No significant differences were observed in LV morphology (LV mass and relative wall thickness), cardiac output and parameters of LV systolic function between patients on suppressive therapy and controls. When compared with controls, patients with exogenous SCH had a significantly impaired longitudinal protodiastolic strain, SR and strain diastolic index but preserved radial strain and SR function. Conclusions In subjects with SCH at the early phase of TSH-suppressive therapy, evidence of isolated longitudinal LV diastolic dysfunction was observed, despite a normal LV morphology. Further prospective studies to clarify the prognosis of picking-up early diastolic dysfunction in asymptomatic patients are needed before serial measurements could be recommended.

Assessment of every hypertensive patient must include the search for kidney disease, i.e. elevated serum creatinine and proteinuria. Antihypertensive therapy may attenuate both the risk of progression toward renal failure and the cardiovascular risk associated with chronic kidney disease, albeit the cause or the consequence of hypertension. Any alteration in renal function will promote salt-sensitivity of blood pressure and increase the deleterious effects of salt intake on target organ damage. The goal of antihypertensive therapy in patients with chronic kidney disease is first to reduce systolic blood pressure below 130 mmHg. The second goal is to lower urinary protein excretion to less than 0.5 g per day. The presence of proteinuria calls for blockers of the renin-angiotensin system among antihypertensive drugs. Global risk management (i.e. fighting tobacco, obesity, dyslipemia) will reduce the renal as well as the cardiovascular risk.

Experimental and clinical data suggest that primary aldosteronism (PA) may be associated with cardiovascular hypertrophy and fibrosis, in part independent of the BP level. Whether PA may also result in specific deleterious effects on the kidneys was less studied. In 25 patients with tumoral PA, renal studies (urinary excretion of proteins, GFR, and effective renal plasma flow [ERPF], as clearances of technetium-labeled diethylene triaminopentaacetic acid and 131I-ortho iodohippurate, respectively) were performed both before and 6 mo after surgical cure. A control group consisting of patients with essential hypertension (EH) was studied before and after 6 mo of antihypertensive therapy. At baseline, PA and EH patients were similar with respect to demographic data, duration and level of hypertension, and GFR and ERPF. Urinary excretion of albumin and beta2 microglobulin were higher in PA than EH (88 +/- 26 versus 39 +/- 12 and 0.91 +/- 0.23 versus 0.26 +/- 0.19 mg/24 h, respectively; both P < 0.05). Adrenalectomy was followed by a decrease in arterial BP (by 28 +/- 3/13 +/- 2 mmHg), urinary excretion of albumin and beta2 microglobulin (by 48 +/- 19 and 0.53 +/- 0.21 mg/24 h, respectively), and GFR and ERPF (by 15 +/- 3 and 54 +/- 15 ml/min per 1.73 m(2), respectively). In EH, a similar decrease in pressure was associated with a decrease in albuminuria but no change in GFR or ERPF. In 17 of the 25 PA patients who received a 6-mo treatment of spironolactone, both GFR and ERPF decreased in parallel with BP, similar to what was observed after surgery. These data suggest that PA was associated with relative hyperfiltration, unmasked after suppression of aldosterone excess.

OBJECTIVES To assess the influence of sodium intake on the two components of arterial blood pressure [mean blood pressure (MBP) and pulse pressure] and left ventricular mass (LVM) in normotensive subjects and never-treated hypertensive patients. METHODS Blood pressure, LVM (M-mode echocardiography) and sodium excretion as an index of dietary sodium were measured in 459 males and 396 females, aged 14-93 years, with elevated (63% of population) or normal blood pressure. RESULTS Because pulse pressure decreased with age up to approximately 40 years of age, and increased thereafter, analysis was undertaken separately in 438 young (age < or = 40 years) and 417 middle-aged to elderly subjects. Before age 40 years, only pulse pressure was independently and positively influenced by urinary sodium excretion. After age 40 years, MBP and LVM index but not pulse pressure were positively influenced by urinary sodium excretion. When men and women were analysed separately according to tertiles of urinary sodium excretion, pulse pressure adjusted for MBP and age increased from the first to the third tertile of urinary sodium excretion in males (P < 0.03), but not in females. CONCLUSIONS The influence of sodium intake on pulse pressure was found in the younger subjects of both males and females and only in men older than 40 years.

International audience; Background: Bone-vessel interaction in chronic renal failure remains poorly understood and could be driven by bone remodeling factors including osteoprotegerin (OPG), fibroblast growth factor 23 (FGF23), parathormone and vitamin D. Only few data are available in renal transplantation. The aim of this study was to investigate the relationship between bone remodeling factors and large artery function in renal transplant patients.Methods: 89 renal transplant patients were enrolled in this cross-sectional study. Carotid to femoral pulse wave velocity (PWV) and central augmentation index (AIx) were determined as an estimation of large artery function. Blood samples were collected for measurement of vascular risk markers. Independent predictors were identified by multivariate linear regression through backward feature selection using Akaike's information criteria.Results: At multivariate analysis, age (p < 0.001) and systolic arterial pressure (p = 0.003) were significantly associated with PWV but not AIx. In addition, both elevated blood concentrations of 1.25(OH)2 vitamin D (p = 0.013) and OPG (p = 0.047) were still significantly related to high PWV.Conclusions: These results underline that age and mean arterial pressure are the main determinants of PWV following renal transplantation. Among bone remodeling biomarkers, plasma OPG and active vitamin D were the strongest determinants of arterial stiffness.

In addition to its widely contested influence on arterial pressure, dietary sodium may exert some nonpressure-related effects on left ventricular mass in humans. In the present study, we hypothesized that sodium intake (estimated by two consecutive measurements of 24-h urinary sodium excretion) may amplify the effect of arterial pressure on target organ damage (ie, left ventricular mass and microalbuminuria) in a large group of normotensive subjects and patients with never-treated uncomplicated essential hypertension. Left ventricular mass (M-mode echocardiography) and urinary albumin excretion were assessed in 839 subjects (471 men and 368 women) aged 15 to 70 years, with elevated (60%) or normal arterial pressure. In the entire population, multivariate analysis indicated that the relationship between urinary sodium excretion and left ventricular mass index (beta = 0.02, P < .01) as well as urinary albumin excretion (beta = 0.001, P < .0001) was independent from sex, age, body mass index, and systolic arterial pressure. When subjects were divided into quintiles according to urinary sodium excretion, left ventricular mass index and urinary albumin excretion increased significantly from the lowest to the highest quintile in both genders, despite similar values of systolic arterial pressure. The slope of the regression line linking systolic arterial pressure to left ventricular mass index (in men) and urinary albumin excretion (in the entire population) obtained within each quintile of urinary sodium excretion, progressively and linearly increased from the lowest to the highest quintile. These results suggest that sodium intake may amplify the effect of arterial pressure on both the left ventricle and the kidney, and thus suggest that dietary sodium may be an independent factor of cardiovascular risk.

Renal function is thought to decrease with age in the general population, but the determinants of this age-associated evolution are poorly understood. Hypertension and diabetes mellitus, two leading causes of chronic renal failure in the elderly, may accelerate this decline.Urinary clearances of [99mTc]diethylene triaminopentaacetic acid (DTPA) (glomerular filtration rate) and [131I]hippuran (effective renal plasma flow) were assessed in 227 never-treated essential hypertensives aged 20-69 years. Based on the oral glucose tolerance test, the study population consisted of 4% patients with previously unknown diabetes mellitus, 24% with impaired glucose tolerance and 72% with normal glucose tolerance.When the population of 218 non-diabetic subjects was considered, glomerular filtration rate was inversely correlated with age and arterial blood pressure, and positively correlated with effective renal plasma flow, filtration fraction and fasting plasma glucose. In multivariate analysis, age and blood pressure were independent determinants of renal plasma flow, whereas renal plasma flow, age and fasting plasma glucose were independent determinants of glomerular filtration rate. The slope of the regression line relating glomerular filtration rate to age was steeper in patients with impaired glucose tolerance than in those with normal glucose tolerance (-1.52 +/- 0.28 versus -0.65 +/- 0.12, P0.01).These results suggest that impaired glucose tolerance, which is seldom searched for in patients with essential hypertension, may be an important determinant of the age-associated decline in renal function.

Summary: Irbesartan (SR 47436, BMS 186295) is an imidazole derivative that specifically binds to the angiotensin type 1 receptor. The purpose of this study was to assess the inhibitory effect of irbesartan on the pressor action of exogenous angiotensin II in healthy subjects, to evaluate the dose dependency and duration of this inhibition, and to determine the effect of irbesartan on plasma components of the renin-angiotensin system. Forty-two healthy male volunteers maintained on ad libitum sodium intake were enrolled in a randomized, double-blind, placebo-controlled, parallel-design, dose-ranging study. On 2 study days 1 week apart, volunteers were given either a placebo or the active drug at one of the chosen doses (5, 25, 50, 75, 100, 150, or 300 mg). The pressor effects of an individually titrated test dose of exogenous angiotensin II as well as plasma levels of angiotensin II, active renin, aldosterone, and treatment drug were determined before and throughout the 24 h after drug administration. The inhibitory effect of irbesartan on the pressor response to angiotensin II was observed within 1 h after dosing, peaked between 2 and 4 h, and lasted more than 24 h for doses of 25 mg and more. The effect was clearly dose related. Two and 24 h after administration of irbesartan, 300 mg, the response of arterial blood pressure (systolic and diastolic) to a given dose of angiotensin II was reduced by approximately 100% and 60%, respectively. Plasma concentrations of angiotensin II and active renin increased markedly after irbesartan administration, whereas plasma concentrations of aldosterone decreased. No evidence was found that the high levels of circulating angiotensin II observed after irbesartan administration could override the inhibitory effect of irbesartan on any of the measured parameters up to 24 h after dose. In conclusion, irbesartan appears to be a well-tolerated, orally active, potent antagonist of the renin-angiotensin system in men.

Abstract —The determinants of the increase in arterial blood pressure associated with the use of estrogen-progestogen oral contraceptives (OC) remain poorly known. The purpose of this study was to assess the renal characteristics and the role of the renin-angiotensin system in women with OC-associated hypertension. Urinary clearances of technetium-labeled diethylene triaminopentaacetic acid (glomerular filtration rate) and 131 I-ortho iodohippurate (effective renal plasma flow) were estimated before and after acute administration of captopril in 38 women who became hypertensive while taking OC, 38 non-OC users with essential hypertension matched for age, body mass index, and level of blood pressure, and 38 normotensive women (19 with and 19 without OC). Plasma renin activity was higher in OC hypertensives when compared with those with essential hypertension, but captopril-induced changes in blood pressure and renal hemodynamics and function were similar in both groups. In addition, 24-hours urinary albumin excretion was increased in OC users when compared with nonusers with similar arterial blood pressure. In 13 hypertensive women followed up for 6 months after OC withdrawal, a decrease in plasma renin activity, blood pressure, and glomerular filtration rate but no significant change in urinary albumin excretion and captopril-induced changes in blood pressure and renal hemodynamics were observed. These results indicate that the use of OC is associated with an increased albuminuria and no evidence of a prominent role for the renin-angiotensin system in the maintenance of high blood pressure and renal hemodynamics when compared with non-OC users with essential hypertension.

BACKGROUND Chronic cyclosporine (CsA) nephropathy, which has been unequivocally documented in recipients of heart, heart-lung, liver, or bone marrow transplants, as well as in nontransplant situations, usually results in a progressive deterioration of renal function. In this study, we assessed the potential reversibility of chronic CsA nephropathy in renal transplant recipients. PATIENTS AND METHODS Twenty-three renal transplant patients with biopsy-proven CsA nephropathy associated with long-term CsA administration (27+/-4 months) were followed up for more than 2 years after CsA reduction (18/23 patients) or withdrawal (5/23 patients) and addition of azathioprine. Changes in effective renal plasma flow and glomerular filtration rate were assessed before and 2 years after CsA reduction, whereas serum creatinine, proteinuria, blood pressure, and CsA concentrations were monitored up to 5 years. RESULTS At 2-year follow-up, glomerular filtration rate increased from 40+/-3 to 47+/-4 (P

Atrial natriuretic peptide (ANP) lowers mean arterial pressure (MAP) and increases hematocrit through reduction in plasma volume caused by a transcapillary shift of plasma fluid and protein toward the interstitium. We examined the consequences of blockade of the dopaminergic and adrenergic systems on the hypotensive and hemoconcentrating responses to ANP. Changes in MAP, hematocrit, and plasma protein concentration (PPC) were measured in anesthetized acutely binephrectomized rats, during infusion of ANP alone (1 microgram.kg-1.min-1 for 45 min) or in the presence of haloperidol (20 micrograms.kg-1.min-1), phentolamine (15 micrograms.kg-1.min-1), or propranolol (10 micrograms.kg-1.min-1). Infusion of ANP reduced MAP by 8.6 +/- 1.3% and increased hematocrit by 9.0 +/- 0.6% (both p0.005 vs. vehicle). PPC increased (4.4 +/- 0.6%; p0.005 vs. vehicle) significantly less than hematocrit, indicating extravasation of proteins. The ANP-evoked reduction in MAP was not affected in haloperidol- or phentolamine-treated rats (-8.8 +/- 2.3 and -10.5 +/- 2.4%, respectively; both p0.005 vs. vehicle) but was abolished in propranolol-treated rats (+3.2 +/- 1.3%; p = ns vs. vehicle). The ANP-induced increase in hematocrit was slightly attenuated in haloperidol-, phentolamine-, and propranolol-treated rats (7.5 +/- 0.7, 7.3 +/- 0.8, and 6.0 +/- 1%, respectively). In addition, the coefficient of reflection, an index of the permeability to proteins, was higher in these three groups (0.41 +/- 0.06, 0.49 +/- 0.08, and 0.57 +/- 0.14, respectively) than in control rats infused with ANP (0.27 +/- 0.03), indicating an attenuation of the ANP-induced extravasation of proteins. Thus, in binephrectomized rats, the hypotensive activity of ANP requires a beta-adrenergic component, whereas its hemoconcentrating action is, at least in part, dependent upon dopaminergic and adrenergic activation.

In addition to factors such as protein intake or hyperlipidemia, hypertension contributes to the progressive deterioration of renal function in experimental animal models of renal disease, and has a prominent role in the imbalance of intrarenal hemodynamics. Reduction of arterial pressure was shown to alter the course of human chronic renal disease. In patients with diabetic as well as nondiabetic nephropathy, the lowering of proteinuria by angiotensin-converting enzyme inhibitors is greater than that observed with other antihypertensive drugs and appears to be independent of blood pressure control alone, whereas albuminuria may be unaffected or worsened during nifedipine treatment. Angiotensin-converting enzyme inhibitors may afford better protection than conventional treatment at various stages of diabetic nephropathy and prevent the evolution from incipient to overt nephropathy. In patients with nondiabetic renal disease, no unequivocal evidence exists for such a protective effect. In renal transplant recipients receiving cyclosporine, converting enzyme inhibitors and calcium antagonists are equally effective in the control of hypertension and both leave unaltered the glomerular filtration rate. It remains to be demonstrated, using adequate study designs, whether a particular class of agent is superior to another in patients with chronic renal disease.

Objective Both atrial natriuretic peptide (ANP) and the dihydropyridine derivative nicardipine lower arterial pressure and induce a shift of plasma fluid from the vascular towards the interstitial compartment. Because some calcium antagonists increase the plasma concentration of ANP, and the effect of ANP on transcapillary fluid shift requires the presence of angiotensin II, we examined the consequences of blocking the ANP and renin-angiotensin systems on the hypotensive and haemoconcentrating effects of nicardipine. Methods We evaluated the effects of 45-min 0.1 or 1 micrograms/kg per min nicardipine infusion on arterial pressure and haematocrit in anaesthetized, acutely binephrectomized Sprague-Dawley rats. Results Infusion of nicardipine resulted in a dose-dependent decrease in arterial pressure. Haematocrit increased by an amount corresponding to the decrease in plasma volume calculated for the relevant dose. In the presence of monoclonal anti-ANP antibodies the nicardipine-induced changes in haematocrit and arterial pressure were not affected. In rats pretreated for 2 weeks with the angiotensin converting enzyme inhibitor enalapril, as well as in rats receiving the angiotensin II receptor antagonist losartan acutely, the nicardipine-induced increase in haematocrit was abolished. In enalapril-treated rats the increase in haematocrit was entirely restored when angiotensin II was infused at a subpressor dose. The nicardipine-induced decrease in arterial pressure was not affected by pharmacological blockade of the renin-angiotensin system. Conclusions These results demonstrate that the transcapillary shift of fluid induced by nicardipine is independent of ANP and requires the presence of a functional renin-angiotensin system, whereas its hypotensive action is independent of both ANP and angiotensin II.

Effect of monoclonal anti-ANP antibodies on the acute functional adaptation to unilateral nephrectomy. The role of endogenous atrial natriuretic peptide (ANP) in the immediate response of sodium excretion to unilateral nephrectomy (UNX) was investigated in anesthetized euvolemic rats through measurement of UNX-induced change in plasma ANP concentration and the response of the remaining kidney to UNX following administration of monoclonal anti-ANP antibodies. The circulating ANP levels almost tripled (from 23 ± 4 to 66 ± 13 fmol/ml, P < 0.01) within two minutes after UNX, whereas no change resulted from sham intervention. In the control group receiving vehicle injection, UNX resulted in a twofold increase in urinary sodium excretion (from 1.39 ± 0.25 to 2.88 ± 0.28 µmol/min, P < 0.01) related to a decrease in the fractional reabsorption of sodium at both proximal and distal sites (estimated from fractional excretion of lithium). Urinary excretion of cyclic guanosine 3′-5′-monophosphate (cGMP) increased as well, but glomerular filtration rate did not change. In addition, UNX was associated with a short-lived (

In essential hypertension, the regression of left ventricular hypertrophy is an important goal of treatment. In addition to treatment-associated changes in blood pressure (BP), the roles of other determinants of left ventricular hypertrophy regression, including dietary sodium intake, deserve investigation. In the present study, the change in echographic left ventricular mass index (LVMI) was assessed in 182 patients with never-treated essential hypertension at baseline and after 3 years of treatment by angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists given at recommended doses and associated with other antihypertensive agents. Treatment was associated with satisfactory control of BP (

To determine whether urinary sodium excretion (a rather rough estimate of sodium intake) can influence left ventricular mass independently of arterial pressure, 91 untreated subjects with essential hypertension and 50 normotensive subjects of similar age were studied. Left ventricular mass index (M-mode echocardiography) was positively correlated with urinary sodium excretion in hypertensive (r = 0.22, P less than 0.01) as well as normotensive subjects (r = 0.22, P less than 0.05), and systolic arterial pressure was correlated only in hypertensive subjects (r = 0.23, P less than 0.01). When hypertensive subjects were divided into groups with appropriate or inappropriate left ventricular mass by reference to a theoretical optimal left ventricular mass for each subject's level of systolic arterial pressure, left ventricular mass was appropriate in 68% and inappropriate in 32% of subjects. Urinary sodium excretion was higher in subjects with inappropriate left ventricular mass compared with those with appropriate left ventricular mass. In conclusion, sodium excretion may be an important modulator of the influence of arterial pressure on the left ventricle in normotensive subjects and subjects with essential hypertension.

Background. Pulse pressure (PP), which reflects the pulsatile component of the blood pressure (BP), is known as a major predictor of cardiovascular events and death. In the elderly and type 2 diabetic patients, PP is associated with low glomerular filtration rate and albuminuria. Because kidney allograft survival is closely related to BP levels, we investigated the impact of early high PP, systolic, diastolic, and mean arterial BP on kidney allograft survival. Methods. Renal hemodynamic and function studies using isotopic methods were prospectively performed in 493 renal transplant patients at 3 months posttransplantation to determine the impact of the different BP components on allograft survival using a proportional hazard model. Results. After a median follow-up of 6.3 years, 91 allografts were lost. High PP was associated with high systolic, diastolic, and mean arterial pressure, heart rate, recipient age, glycemia, and low glomerular filtration rate. Moreover, PP emerged as the strongest BP component influencing overall and death-censored kidney allograft survival. Conclusion. High PP is an early marker of poor allograft outcome that could be corrected by therapeutic intervention.

The effects of cyclosporine A treatment on arterial pressure and renal function were assessed in 11 young patients with type I diabetes of short duration. Cyclosporine was started at 7.5 mg/kg/day, progressively decreased to 6.3 mg/kg/day at 6 months, and then continued at a lower dose (4.1 mg/kg/day) for an additional 3 months in patients in whom remission of insulin dependency was obtained (n = 6). After 3 months of cyclosporine, a slight but significant increase in arterial pressure (+5.2 +/- 1.5 mm Hg), a rise in renal vascular resistance (approximately 20%), a decrease in glomerular filtration rate (approximately 25%), and a fall in filtration fraction were observed. Such changes were sustained after 6 and eventually 9 months of therapy. The decrease in glomerular filtration rate observed during cyclosporine treatment contrasted with the lack of change in simultaneously estimated creatinine clearance; in fact, the creatinine clearance/glomerular filtration ratio increased from 1.07 +/- 0.05% to 1.33 +/- 0.09% within 3 months of cyclosporine therapy, thus suggesting an enhanced tubular secretion of creatinine. Plasma renin activity and urinary excretion of kallikrein decreased significantly (approximately 50%), whereas plasma aldosterone concentration remained unaltered and plasma concentration of potassium increased during cyclosporine therapy. These changes were observed in the presence of a constant urinary excretion of sodium and potassium and a constant body weight. All parameters returned to pretreatment values within 3 months after cessation of cyclosporine. These results indicate that cyclosporine given for 6-9 months at a moderate dose causes a deleterious but reversible effect on arterial pressure and renal function in young diabetic patients.

Arterial pressure is within 'normal' limits in most diabetic patients with or without microalbuminuria and elevated in 70% of patients with overt diabetic nephropathy. An abnormal increase in the level of urinary excretion is a strong predictor of the subsequent development of overt diabetic nephropathy and ultimately renal insufficiency. Correction of hypertension is associated with a reduction in the rate of decline of the glomerular filtration rate in overt diabetic nephropathy. In patients with microalbuminuria, short-term studies have shown that angiotensin converting enzyme (ACE) inhibitors, in contrast with calcium antagonists, decrease urinary albumin excretion. Additional studies assessing the long-term effect of antihypertensive agents on the evolution of early diabetic nephropathy are needed. The superiority of ACE inhibitors over other antihypertensive agents in the treatment of overt or early diabetic nephropathy remains to be demonstrated. In addition to arterial pressure control, it is possible that optimal glycaemic control in addition to the modification of protein intake, dietary sodium and serum lipid profile may alter the course of diabetic nephropathy.

In large epidemiological studies and using serum creatinine or estimates of glomerular filtration rate (GFR), blood pressure has emerged as a predominant determinant of the age-associated decline in renal function.The present longitudinal study (median follow-up period of 5.8 years) was conducted in 132 never-treated patients with essential hypertension at baseline. The effect of treatment on the GFR and effective renal plasma flow, estimated by urinary clearances of isotopic markers, was assessed.Satisfactory control of hypertension (140/90 mmHg) was achieved in 57% of the population. During follow-up, the yearly change in the GFR was -1.72+/-0.21 ml/min per year (mean+/-SEM). In univariate regression analysis, the change in the GFR was correlated with baseline pulse pressure (r=-0.27, P=0.002), whereas no influence of systolic, diastolic or mean blood pressures, as well as baseline albuminuria or left ventricular mass index, was found. Multivariate logistic regression analysis showed that only baseline pulse pressure conveyed a significant odds ratio of accelerated decline of GFR (median of 1.5 ml/min per year), independently of age, baseline GFR, mean blood pressure and other known cardiovascular risk factors. No influence of the type of antihypertensive treatment (64% of the population had received angiotensin-converting enzyme inhibitor) was detected.Pulse pressure (a marker of arterial stiffening) is suggested as an independent determinant of the treatment-associated decline in renal function in essential hypertension. No influence of target organ damage (albuminuria of left ventricular hypertrophy) was detected.

In the past decade, pulse pressure has emerged as a strong predictor of cardiovascular morbidity and mortality. During aging, elevation of pulse pressure is a consequence of stiffening of the arterial wall. The relationship between pulse pressure and the renal aging process was studied in a cohort of 212 patients with never-treated isolated systolic hypertension. Glomerular filtration rate and effective renal plasma flow were measured using constant infusion of technetium 99m ( 99m Tc)-DTPA and 131 I-ortho-iodohippurate, respectively, and timed urine collections. The relationship between pulse pressure and renal function was studied using a linear regression model in the total population and in 40 to 49, 50 to 59, and 60 years and older age categories. In the whole population, there was an inverse relationship between pulse pressure and glomerular filtration rate; however, this relation did not persist after adjustment for age. In fact, the inverse relationship between pulse pressure and glomerular filtration rate was only present in patients 60 years of age or older. This relationship in elderly patients remained after adjustment for age, gender, MAP, and cardiovascular risk factors ( P =0.006). It is suggested that pulse pressure, a marker of arterial stiffening, may have a detrimental influence on the age-related decline in glomerular filtration rate, after 60 years of age in patients with never-treated isolated systolic hypertension.

Blood pressure is a marker of elevated risk for cardiovascular disease, even within the normotensive range. The present study evaluates cardiorenal modifications observed in normotensive (P

Renal parenchymal disease and renovascular abnormalities are the most common causes of secondary hypertension. In clinical practice, a search for renal disease (i.e., proteinuria, abnormal urinary sediment, increased serum creatinine) should be undertaken in the presence of any newly diagnosed hypertension; however, only selected patients should be screened for renovascular disease. In recent years, the challenge in the management of patients with renal parenchymal disease has focused on the influence of strict control of hypertension on the rate of deterioration of renal function with time. In several experimental models, the use of antihypertensive agents has proved efficient in preventing the decline in renal function as well as the extent of glomerulosclerosis; interestingly, all antihypertensive medications were not equally effective in this regard. A number of questions remain unsettled in humans: Can adequate control of blood pressure slow down renal deterioration? Which drug should be used? What is the optimal level of arterial pressure? Although ischemic renovascular disease has recently emerged as an important cause of renal failure, the potential of revascularization to improve or preserve renal function is still a matter of debate.

Abstract The existence of a direct relationship between body mass and arterial pressure is well recognized; however, the effect of obesity on known target organs of hypertension is not clearly understood. We undertook the present studies to assess the influence of obesity on renal function and urinary albumin excretion in 40 normotensive subjects and 80 never-treated hypertensive patients matched for age, sex, arterial pressure level, and known duration of hypertension in whom an oral glucose tolerance test was within normal limits. Glomerular filtration rate and effective renal plasma flow (expressed as absolute values or values normalized for height) were increased in overweight compared with lean subjects whether normotensive or hypertensive. Glomerular filtration rate was positively correlated with protein intake (as assessed from urinary excretion of urea) and fasting serum insulin level. Urinary excretion of albumin but not IgG and β 2 microglobulin was higher in hypertensive patients compared with normotensive subjects. The overweight condition clearly enhanced the influence of arterial pressure on albuminuria; in fact, a steeper regression line between albumin excretion rate and arterial pressure was found in overweight compared with lean subjects. These results indicate that the overweight condition is associated with renal hyperfiltration and hyperperfusion, irrespective of the presence of hypertension, and that obesity magnifies the effect of hypertension on albuminuria, thus raising the possibility of an increased susceptibility of obese hypertensive patients to the development of renal damage.

Converting-enzyme inhibitor versus calcium antagonist in cyclosporine-treated renal transplants. The influence of antihypertensive treatment on the long-term evolution of arterial pressure and renal function was studied in a prospective controlled trial conducted in renal transplant recipients treated by cyclosporine. Within six months after transplantation, patients were randomly allocated to treatment by the angiotensin-converting enzyme inhibitor, lisinopril (ACEI, alone or associated with frusemide; N = 14), or the calcium antagonist, nifedipine (CA, alone or associated with atenolol; N = 11). Glomerular filtration rate (TcDTPA clearance) and effective renal plasma flow (hippuran clearance) as well as 24-hour urinary excretion of electrolytes and albumin were estimated at about 1 and 2.5 years of follow-up. Before initiation of antihypertensive therapy, the two groups were similar with regards to mean arterial pressure (119 ± 2 vs. 120 ± 4mm Hg), effective renal plasma flow (285 ± 26 vs. 248 ± 33 ml/min/1.73 m2) and glomerular filtration rate (59 ±4 vs. 61 ± 8 ml/min/1.73m2 in the ACEI and CA groups, respectively). Both ACEI and CA treatments were associated with no change in renal function, a similar change in mean arterial pressure (ACEI -18 ± 3; CA -13 ± 5 mm Hg) and identical trough blood levels of cyclosporine. Urinary albumin excretion did not change significantly in any groups. Of interest, only in the ACEI group did filtration fraction significantly decrease (from 0.22 ± 0.01% to 0.19 ± 0.01% at final studies). These results indicate that in cyclosporine-treated transplant recipients, a satisfactory control of hypertension is obtained by chronic ACEI, which is as effective on arterial pressure as a combination of CA and atenolol. A consistent reduction of arterial pressure by either treatment seems to afford a similar degree of renal protection in long-term cyclosporine treated patients.

HYPERTENSION AND RENAL DISEASE: In experimental models of renal disease not only protein intake and hyperlipidaemia but also hypertension may contribute to the progressive deterioration in renal function; in these models an imbalance in intrarenal haemodynamics appears to be a particularly important factor. ANTIHYPERTENSIVE THERAPY: A reduction in arterial pressure can alter the course of human chronic renal disease. However, it is not clear whether any one class of antihypertensive drug is superior to any other class in these patients. Angiotensin converting enzyme (ACE) inhibitors may prevent the progression from incipient to overt diabetic nephropathy and afford better protection than conventional treatment. In patients with non-diabetic renal disease there is no unequivocal evidence for a protective effect. In renal transplant recipients, mainly those taking cyclosporine, ACE inhibitors are equally effective compared to calcium antagonists in the control of hypertension, but their renal effects in transplant recipients without renal artery stenosis have not yet been assessed.

Infrarenal aortic cross-clamping is associated with impairment of renal hemodynamics due to vasoconstriction, the mechanism of which remains under debate. To assess the renal effect of two potent renal vasodilators (enalapril, a converting enzyme inhibitor, and nicardipine, a calcium antagonist), 24 patients scheduled for reconstructive aortic surgery were randomly allocated to one of three treatment groups (n = 8 each) and received either a placebo, nicardipine, or enalapril. Anesthesia consisted of flunitrazepam, fentanyl, pancuronium, and, occasionally, droperidol. Although aortic cross-clamping was associated with no change in mean arterial blood pressure, decreased cardiac output and increased systemic vascular resistance occurred in control patients (33% and 43%, respectively, both P less than 0.05 versus baseline) and nicardipine-treated patients (51.7% and 67.7%, respectively, both P less than 0.05 versus baseline); however, changes in cardiac output and systemic vascular resistance failed to reach significance in enalapril-treated patients. Glomerular filtration rate (technetium 99-diethylenetriaminepentacetic acid clearance) and effective renal plasma flow (iodo-Hippuran 131 clearance) decreased for the duration of aortic cross-clamping in control patients (42.9% and 18.5%, respectively, both P less than 0.05 versus baseline) and enalapril-treated patients (34.0% and 38.1%, respectively, both P less than 0.05 versus baseline), but no change was observed in nicardipine-treated patients. These results suggest that the reninangiotensin system is not an important determinant of the renal vasoconstriction associated with aortic cross-clamping. In contrast, renal dysfunction may be alleviated by the dihydropyridine derivative nicardipine, which probably acts at the level of the preglomerular resistance vessels.

To further investigate the mechanism(s) of the exaggerated natriuretic response of hypertensives to volume expansion (VE; 1,800 ml iv isotonic saline over 3 h), the plasma levels of immunoreactive atrial natriuretic peptide (ANP) were measured in 11 normal subjects (NT) and 12 patients with mild essential hypertension (HT). NT and HT groups were similar with respect to age and basal levels of renin, aldosterone and ANP (34.5 +/- 5.5 in NT and 32.5 +/- 6.3 pg/ml in HT, mean +/- SE). In response to VE, ANP increased to the same extent in both groups (a change of 19.3 +/- 5.2 in NT and of 22.2 +/- 7.1 pg/ml in HT) despite the finding of an exaggerated natriuretic response to VE in essential hypertension (36 +/- 3.5 in NT and 54.9 +/- 6.3 nmol/3 h in HT, P less than 0.02). In addition, the fall in hematocrit and serum protein associated with saline infusion was less marked in HT than NT. The change in ANP induced by VE was inversely correlated with the percent fall in hematocrit and the increment in the fractional excretion of sodium in both groups. These observations suggest that ANPs may participate in the control of the renal response to isotonic VE; however they do not support an unequivocal influence of ANP in the exaggerated natriuretic response to VE of patients with essential hypertension.

In order to assess the determinants of renal function deterioration induced by angiotensin-converting enzyme inhibition (ACEI) in renovascular hypertension, studies were performed in patients with bilateral stenosis (BS; n = 12) and stenosis of a solitary kidney (SK; n = 10). Acute administration of captopril was associated with a consistent fall in glomerular filtration rate in 5 of 12 patients with BS and 8 of 10 with SK. Overall, glomerular filtration rate decreased by 22 +/- 7%, while mean arterial pressure decreased by only 8 +/- 2% and renal plasma flow remained unaltered. The ACEI-induced change in glomerular filtration rate was unrelated to blood pressure or basal plasma renin activity, but it was inversely related to pre-ACEI filtration fraction. In a comparative study conducted in 6 BS and 4 SK patients, acute administration of nifedipine was associated with a change in glomerular filtration rate of 13 +/- 5% and no change in renal plasma flow, despite a marked decrease in mean arterial pressure of 19 +/- 4%. In contrast, in the same patients, glomerular filtration rate fell by 23 +/- 12%, renal plasma flow did not change and mean arterial pressure fell slightly by 7 +/- 3% after ACEI.(ABSTRACT TRUNCATED AT 250 WORDS)

The systemic and renal responses to normal volume expansion (1800 ml isotonic saline infused over 3 h) were assessed in 23 patients with essential hypertension after 4-7 days' administration of a placebo or the calcium antagonist nitrendipine (20 mg three times a day) or the angiotensin converting enzyme (ACE) inhibitor captopril (50 pressure mg three times a day). Each drug treatment was associated with a fall in blood pressure of the same magnitude. Treatment with captopril was associated with a significant volume dependence of blood pressure and a blunting of the exaggerated natriuresis of hypertension (71 +/- 16 on placebo and 47 +/- 12 mmol/3 h on captopril; P less than 0.01). Treatment with nitrendipine did not affect the change in blood pressure associated with volume expansion, but significantly enhanced the natriuretic response to volume expansion (61 +/- 8 on placebo and 90 +/- 16 mmol/3 h on nitrendipine; P less than 0.01). No alterations in baseline or volume expansion-induced changes in the glomerular filtration rate or in plasma renin activity were observed during treatment with nitrendipine. Therefore, the exaggerated natriuresis of essential hypertension was blunted by the ACE inhibitor and enhanced by the calcium antagonist, despite a similar reduction in pre-expansion arterial pressure.

Renin-angiotensin system activation is suspected of being involved in postcoronary surgery hypertension, but appears to be useful in maintaining blood pressure during anesthesia and cardiopulmonary bypass. To clarify these points, 19 patients were compared: ten as a control group and nine who received captopril during two days before surgery. Anesthesia was the same for the two groups, and cardiopulmonary bypass ensured nonpulsatile flow rates. Anesthesia induced a slight decrease in the mean arterial blood pressure of the treated group (91.1 +/- 3.3 mm Hg to 83.3 +/- 3.9 mm Hg), which did not occur in the control group (89.9 +/- 5.8 mm Hg to 89.7 +/- 4.9 mm Hg). During cardiopulmonary bypass, the mean arterial blood pressure was maintained at comparable levels in the two groups (65.6 +/- 3.5 mm Hg in the control group, 72.6 +/- 3.0 mm Hg in the treated group), with same pump flow rates. After cardiopulmonary bypass, the mean arterial blood pressure returned nearly to prebypass values. Postoperatively, three patients in the control group and four in the treated group developed hypertension. Thus, preoperative renin-angiotensin system blockade by a converting-enzyme inhibitor did not impair blood pressure regulation during anesthesia and cardiopulmonary bypass, but failed to prevent hypertension following coronary surgery.

In these studies, the effect of a 6-wk treatment by placebo, the calcium-channel blocker nifedipine, or the converting-enzyme inhibitor captopril was assessed in normotensive patients with insulin-dependent diabetes and incipient nephropathy. In response to captopril and nifedipine, arterial pressure decreased slightly and to a similar extent. These drugs resulted in opposite effects on urinary excretion of albumin [i.e., increase in urinary albumin excretion (UAE) by 40% during nifedipine treatment and decrease by 40% during captopril treatment]. No change in UAE was observed in the p acebo group. This observation of opposite changes in U E i the presence of a similar fall in arterial pressur suggests that the effects of captopril and nifedipine o UAE result from some difference in their intrarenal a ction. The data do not present recommendations for the use or disuse of captopril or nifedipine in such a group of patients and do not allow extrapolation to hypertensive diabetic subjects well controlled by other conventional antihypertensive agents.

Microalbuminuria is a reliable predictor of the eventual development of overt diabetic nephropathy and blood pressure is known to accelerate the course of this nephropathy. In the present studies, the effect of a 6-week treatment by placebo (n = 7), nifedipine (n = 7) and captopril (n = 8) on renal function and urinary excretion of albumin (UAE) was investigated in normotensive, insulin-dependent, diabetic patients with incipient nephropathy (UAE greater than 15 micrograms/min). No change in arterial pressure, renal function or UAE was observed in the placebo group. In response to captopril and nifedipine, mean arterial pressure decreased slightly and similarly in both groups. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) increased to a similar extent in the nifedipine group, thus resulting in no change in filtration fraction (FF). In response to captopril, GFR was unchanged whilst ERPF increased; as a consequence FF decreased. Opposite changes in UAE were observed in response to the two treatments; UAE decreased by 40% in the captopril group and by 40% in nifedipine-treated patients. These results indicate that intrarenal changes may be crucial with respect to the effect of therapy on UAE. It is suggested that only agents which reduce FF and probably intraglomerular capillary pressure, such as converting enzyme inhibitors, alter UAE and may possibly interfere with the course of incipient diabetic nephropathy in normotensive patients.

Nifedipine, in a slow release preparation, was given at a mean daily dosage of 47 +/- 4 mg to 12 patients with severe hypertension in whom arterial pressure was not satisfactorily controlled (mean arterial pressure 132 +/- 4 4 mm Hg) by the combination of a converting enzyme inhibitor and a diuretic. The addition of nifedipine induced an appreciable decrease in mean arterial pressure of 31 +/- 5 mm Hg and of serum potassium and plasma aldosterone. After adequate control of hypertension and because of severe hypokalemia in some patients, discontinuation of the diuretic was attempted in 10 subjects. After 1.7 +/- 0.5 months of treatment by the converting enzyme inhibitor and nifedipine no change in arterial pressure occurred while serum potassium had returned to normal in most patients. These results show that nifedipine may be useful in patients with a residual rise of arterial pressure when treated by converting enzyme inhibitor plus diuretics; in such patients, however, the serum potassium concentration should be carefully monitored. In addition, our observations suggest that calcium blockers may be an effective alternative to diuretics in patients receiving a converting enzyme inhibitor.

Using binephrectomized anaesthetized rats, we explored the possibility that calcium antagonists may alter the partition of extracellular fluid between plasma and the interstitium, as suggested for atrial natriuretic factor (ANF). The effects of intravenous infusion of synthetic ANF (103-126 ANP; Wy 47.663) and the dihydropyridine derivative nicardipine were assessed by measuring changes in haematocrit and plasma proteins. After a 40-min infusion of ANF or nicardipine, haematocrit increased significantly (9% and 5.4%, respectively). The calculated loss of plasma volume was 15% after administration of ANF and 9.1% after nicardipine compared with 3.9% in rats receiving vehicle only. Plasma proteins increased by only 3.9% (after ANF) and 3.7% (after nicardipine), less than expected for a plasma volume contraction without protein extravasation. Atrial natriuretic factor and nicardipine induced a similarly slight change in mean arterial pressure. These results suggest that nicardipine and ANF both reduce plasma volume by an extrarenal mechanism; part of the fluid shift might be facilitated by an increased vascular permeability to proteins.

Summary In the elderly patient with essential hypertension of long duration or de novo systolic hypertension, the prevalence of co-morbid conditions, be they apparent or not, the burden of associated diseases and the alteration in nutritional status and lifestyle, result in specific problems with regards to hypertension-related target organ damage. Accumulating data suggest that left ventricular (LV) remodelling is a common finding in the normotensive elderly, and that LV hypertrophy (LVH) will herald the development of heart failure in a fraction of patients with either systolic/diastolic or isolated systolic hypertension. Increased arterial stiffness, as well as impaired myocardial relaxation, reduced early diastolic filling and decreased β-adrenergic responsiveness, contribute to the large prevalence of abnormalities in LV function in the elderly hypertensive.The response to exercise is clearly attenuated, and coronary heart disease, although highly prevalent, may be misdiagnosed because symptoms are altered.The elderly hypertensive is exquisitely sensitive to both volume depletion and excessive sodium intake, due to a marked sodium sensitivity of blood pressure (BP). A decline in renal blood flow and glomerular filtration rate (GFR) is a common finding in the elderly. Although structural alterations attributed to age and hypertension may differ, hypertension is often looked upon as an accelerated form of ageing with regards to the heart and the kidney. Lifestyle modifications and initial monotherapy with a low-dose diuretic are warranted in the elderly hypertensive with no co-morbidity; a variety of specific approaches are considered when associated clinical conditions are present. Blockers of the renin-angiotensin system (RAS) may be the preferred first-line agents in many patients with cardiac or renal damage.

Among the many factors that have been implicated in the pathogenesis of myocardial hypertrophy is a sodium effect. In the present study, the influence of dietary sodium, estimated by 24-h natriuresis, on left ventricular mass was assessed in 41 patients with mild essential hypertension who had never been treated. Posterior wall thickness and left ventricular mass, but not left ventricular internal diameter were directly correlated with 24-h natriuresis (r = 0.47 and 0.46; P less than 0.02 and 0.002, respectively). Stepwise multiple regression analysis confirmed that 24-h natriuresis was a determinant of left ventricular mass independently of sex, age, body weight, blood pressure and the duration of hypertension. These results suggest that dietary sodium may play a role in modulating left ventricular mass in untreated hypertensives.

The effect of cyclosporine A therapy on blood pressure and renal function was assessed in 11 young adults with type 1 diabetes of recent onset (7 +/- 1 weeks). Metabolic control and renal haemodynamics and function were evaluated at 3-month intervals before, during and after cessation of a 6-month course of cyclosporine A (initial dose 7.5 mg/kg per day, then adapted on whole-blood trough levels of 401 +/- 45 and 308 +/- 49 ng/ml at 3 and 6 months, respectively). A significant increase in blood pressure (from 117 +/- 2/65 +/- 2 to 122 +/- 2/72 +/- 3 mmHg; P less than 0.01) and a decrease in 99Tc-DTPA (diethylene triaminepentaacetic acid) clearance (124 +/- 6 to 98 +/- 5 ml/min per m2; P less than 0.01) were observed after 3 months of cyclosporine A; both alterations remained unchanged after 6 months. No variation in body weight, 24-h urinary sodium or urinary albumin excretion was observed. Blood pressure and the glomerular filtration rate returned to basal levels 3 months after the cyclosporine A therapy ceased. These results suggest that even moderate doses of cyclosporine A have a reversible deleterious effect on blood pressure and renal function in young diabetic patients.