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Insulin resistance is a critical component underlying the altered glucose homeostasis in a variety of metabolic and non-metabolic disorders. Aging, body fat distribution, obesity, diabetes mellitus or hypertension are well recognized conditions associated with an impaired tissue sensitivity to insulin action. Apart from such constant factors, insulin sensitivity can be acutely modified by independent variables such as physical exercise, dietary factors, alcohol intake or harmless drugs. To evaluate the day-to-day intra-individual variation in insulin sensitivity, glucose homeostasis and lipid profiles, we investigated the insulin sensitivity index (S1) (determined by the minimal model method of Bergman), basal and post-glucose-load insulin and glucose levels, serum total triglyceride and lipoprotein cholesterol fractions in 15 healthy young men (24 +/- 1 year, mean +/- SEM), on two different occasions at an interval of 3 weeks (days 1 and 21), after 3 days of a standard dietary regimen and after an overnight fast. Blood pressure, heart rate, body weight and 24 h urinary sodium excretion were almost identical in the two phases. S1(day 1) varied from 4.2 to 15.8 x 10(-4).min-1 pro microU/ml (mean: 10.2 +/- 0.9) and correlated with S1(day 21) (11.2 +/- 1.2 x 10(-4).min-1 pro microU/ml, r = 0.78, p less than 0.0007). The slope of the relationship did not differ from 1 (1.01, p greater than 0.90), the intercept was close to the origin (0.8, p greater than 0.73) and the coefficient of variation was 14.4%.(ABSTRACT TRUNCATED AT 250 WORDS)

A possible modulating influence of noradrenergic activity on serum lipoproteins was assessed under placebo conditions and following 4 weeks of sympathetic neurone blockade with debrisoquine in 9 normal subjects, 11 patients with mild essential hypertension, 9 normotensive, and 9 hypertensive hemodialysis patients. Plasma norepinephrine (NE) did not differ significantly among groups on placebo and was consistently reduced (P less than 0.05-0.001) by sympathetic blockade. The latter also decreased (P less than 0.05-0.001) plasma total cholesterol (C) as well as low and very low density lipoprotein cholesterol (LDL + VLDL-C) in the three patient groups. In the two dialysis groups, basal levels of plasma triglycerides (Tg) were increased and high density lipoprotein cholesterol (HDL-C) was diminished (P less than 0.01-0.001); sympathetic blockade lowered Tg and raised HDL-C (P less than 0.01-0.001). In normal subjects, sympathetic blockade did not significantly modify plasma lipoproteins. In the three patient groups, significant correlations (r = 0.62 - 0.88; P less than 0.05 - less than 0.001) existed between (a) basal plasma NE and total C or LDL + VLDL-C and (b) debrisoquine-induced changes in NE and changes in total LDL + VLDL-C. These findings suggest that in essential hypertension as well as in hemodialysis patients, the atherogenic C fraction, represented by LDL + VLDL-C, may be modulated by the noradrenergic activity.

Patients with renal functional impairment are prone to develop hypertension and hyperlipidemia, and both abnormalities tend to occur already at an early stage of kidney disease. In 18 patients with mild renal disease (glomerular filtration rate 65 +/- 5 ml/min) and hypertension (mean blood pressure 126 +/- 4 mm Hg), the effect of six weeks of treatment with the loop-diuretic muzolimine on serum lipoproteins was assessed. Compared to placebo values, the diuretic significantly increased serum low-density lipoprotein cholesterol (LDL-C) and apoprotein B (+ 18 and 11%, respectively, P less than 0.005) in 13 men or postmenopausal women, but not in 5 premenopausal women. Serum high-density lipoprotein cholesterol (HDL-C), and total triglycerides or lipoprotein triglyceride fractions were not consistently changed in both subgroups. Thus, the ratio LDL-C/HDL-C was increased from 3.2 +/- 0.3 to 3.9 +/- 0.3 (P less than 0.05) in the men or postmenopausal women, while no such tendency occurred in the premenopausal women (4.1 +/- 0.6 to 3.7 +/- 0.6). Changes in serum LDL-C were not associated with hemoconcentration or alterations in carbohydrate metabolism and were not related to variations in serum potassium or blood pressure. Increased serum levels of the atherogenic LDL-C fraction during diuretic treatment in men or postmenopausal women with renal disease may represent a potentially undesirable effect, particularly since such patients may tend to have hyperlipidemia in the untreated state.

This study was designed to evaluate the role of aldosterone, glomerular filtration and blood pressure on sodium excretion in renal disease. Sodium clearance (CNa), plasma aldosterone (PA), plasma renin activity (PRA), glomerular filtration rate (GF), paraaminohippurate clearance (CPAH) and blood pressure were measured simultaneously in 19 normal subjects, 38 patients with benign essential hypertension, 3 with renal artery stenosis, 48 with chronic glomerulonephritis, 20 with the nephrotic syndrome, 24 with tubulo-interstitial disease and 21 with a renal homograft. CNa was significantly depressed in patients with the nephrotic syndrome. Mean PA and PRA were increased in renal artery stenosis but within the normal range in other groups. CNa correlated inversely with PA in all groups but one (tubulo-interstitial disease). CNa correlated directly with GF in the nephrotic syndrome and with the mean blood pressure (mBP) in chronic glomerulonephritis and tubulo-interstitial disease. PA correlated directly with PRA and inversely with GF or CPAH in most groups. It is concluded that PA is an important determinant of the basal natriuresis in renal disease with the exception of tubulo-interstitial nephropathies. In the nephrotic syndrome sodium retention is largely determined by the interaction of PA and GF. In chronic nephropathies, but not in benign essential hypertension, the fractional sodium excretion is partly blood pressure-dependent. Impairment of renal function is often accompanied by a rise in PA.

In seven patients with uncomplicated essential hypertension the effects of an acute alpha-adrenergic blockade, alone and combined with a chronic beta-adrenergic blockade, on blood pressure, renal function as measured by standard clearance methods, plasma renin activity, and plasma aldosterone were evaluated. Acute alpha-adrenergic blockade with phentolamine (20 mg by intravenous infusion) significantly enhanced the antihypertensive effect of chronic beta-adrenergic blockade with slow-oxprenolol (160 mg/ day X 14 days) (- 14.5% verus - 7.4% for pulse pressure, - 12.4% versus - 6.0% for diastolic pressure, 2 alpha less than 0.05). Under combined adrenergic blockade renal plasma flow increased, glomerular filtration rate and filtration fraction decreased (2 alpha less than 0.05 each), whereas the fractional clearances of sodium, potassium, free water, and solute load remained unchanged. The activation of the renin-angiotensin-axis, elicited by alpha-adrenergic blockade alone, was suppressed by the preceding beta-adrenergic blockade. These findings demonstrate a favourable antihypertensive action of a combined blockade of alpha- und beta-adrenergic receptor sites without untoward side effects on renal function or the renin-angiotensin-axis.

The interrelationships among age, cardiovascular pressor reactivity to intravenously infused norepinephrine (NE) or angiotensin II, and endogenous plasma NE or renin (PRA) levels were evaluated i 31 normal subjects and 37 patients with essential hypertension. In normal subjects both angiotensin II pressor dose and PRA decreased progressively with aging. Angiotensin pressor dose correlated positively with PRA (r = 0.41, P < 0.025) and inversely with age (r = -0.46, P < 0.02). NE pressor dose and basal plasma NE were also positively correlated (r = 0.53, P < 0.005), but the two factors remained largely unchanged with aging. Findings in essential hypertension differed in certain aspects. Angiotensin II pressor dose did not correlate with either basal PRA or age; and pressor doses of NE and angiotensin II tended to be lower in some patients than in normal subjects. These findings indicate that aging is accompanied by a physiologic increase in cardiovascular reactivity to angiotensin II, probably due to a concomitant decrease in circulating renin. The dissociation between angiotensin pressor dose and PRA in essential hypertension suggests an interference from an other factor.

Twenty patients (mean age 49 +/- 4 (SEM) yr) with mild to moderate essential hypertension were studied during placebo conditions, following 6 weeks of chlorthalidone monotherapy and 6 to 28 weeks of combined beta-blocker-chlorthalidone treatment, or vice versa. Compared to chlorthalidone therapy alone, addition of a beta-blocker to this diuretic caused a further blood pressure reduction in 11 patients (Responders); in 9 patients addition of a beta-blocking agent failed to further reduce blood pressure (Non-responders). Supine and upright plasma renin, aldosterone, norepinephrine and epinephrine levels and catecholamine excretion rates were always comparable between Responders and Non-responders. In both groups plasma and urinary norepinephrine or epinephrine values were not significantly altered following addition of a beta-blocker; heart rate and plasma renin activity were decreased in both groups to a similar extent. It is concluded that the antihypertensive mechanism of beta-blockers given to diuretic treated patients with essential hypertension is independant of renin and not associated with changes in plasma or urinary catecholamines.

Glucose loading is known to cause acute suppression of plasma aldosterone and stimulation of plasma renin activity. The relative contribution of variations in circulating angiotensin II to the regulation of aldosterone secretion following glucose loading was assessed in ten normal subjects. The effects of a standard oral glucose loading test (100 g) on plasma concentrations of glucose, insulin, potassium, aldosterone, renin activity and cortisol were studied (a) under basal conditions, and (b) after inhibition of angiotensin II with the converting enzyme inhibitor captopril (50 mg t.i.d. during 3 days). Under basal conditions the acute increase in plasma glucose and insulin after glucose loading was accompanied by a significant decrease (P less than 0.01) in plasma cortisol and aldosterone and by a significant increase in plasma renin activity (P less than 0.01); plasma potassium was decreased slightly but not significantly. Following captopril treatment preloading plasma renin activity was increased significantly, most probably reflecting an effective reduction of angiotensin II. Glucose loading caused a similar suppression of plasma aldosterone, as observed under basal conditions. This observation suggests that renin activation does not substantially contribute to the acute regulation of plasma aldosterone after an oral glucose load.

Responses of blood pressure and plasma catecholamines to intravenous injection of tyramine at increasing dosage (30, 45, and 60 microgram/kg, respectively) were evaluated in 25 normal subjects and 20 patients with mild essential hypertension. Basal plasma norepinephrine and epinephrine concentrations before tyramine injections were similar in the two groups. Following tyramine injection, plasma epinephrine was unchanged. Responses of plasma catecholamines and blood pressure to tyramine were similar in the two groups. Plasma norepinephrine increased significantly 2 min after a dose of 30 microgram/kg, but higher tyramine doses failed to produce a further increase in plasma norepinephrine. In contrast, pressor responses to tyramine were dose-dependent. Maximal pressor responses were observed within 23 min after injection. These findings reveal a dissociation between changes in blood pressure and plasma norepinephrine following injection of tyramine. Lack of steady state may limit the value of tyramine bolus injections as a tool for the quantitation of pressor responsiveness to variations in endogenous sympathetic output. Alternatively, it is possible that the pressor effect of tyramine may be mediated at least in part by a norepinephrine independent mechanism.

The sympathetic system, the body sodium-fluid volume state, the renin-angiotensin system, functional and structural characteristics of the heart and blood vessels, and some other components are important complementary factors in blood pressure regulation. A deviation from the normal equilibrium among these components, with a persisting non-physiologic increase in pressor factor(s) or in the basal vascular tone and/or cardiovascular reactivity to pressor factors, leads to hypertension. This review discusses recent observations and concepts regarding the pathogenesis of essential hypertension and hypertension associated with diabetes mellitus. It focuses on the roles of various pressor factors as well as cardiovascular pressor responsiveness in the genesis of high blood pressure and in the antihypertensive mechanism of diuretic treatment.

Whether and to what extent the sympathetic nervous system participates in the development of essential hypertension has remained largely unclear. The role of the adrenergic effector - cardiovascular response axis in the pathogenesis of essential hypertension was investigated by combined analysis of blood levels, total plasma clearance and cardiovascular pressor effects of norepinephrine (NE). Measurements of plasma NE and blood pressure were performed before, during and after an intravenous infusion of NE at stepwise increasing rates in approximately age and sex-matched groups of 28 normal subjects and 35 patients with essential hypertension. The threshold of the pressor effect of NE was lower in hypertensive than in normal subjects (20 +/- 10 vs. 42 +/- 26 ng/kg min; P < 0.001); but the slope of the dose - resonse curve and basal endogenous plasma NE were in the average similar. Total plasma NE clearance estimated under steady state conditions was similar in normal and hypertensive subjects (5.3 +/- 2.5 vs. 5.4 +/- 2.31/min). NE clearance corrleated inversely with basal plasma NE in normal subjects (r = 0.57; P < 0.005). The plasma half-life of NE was about 2 min. These findings demonstrate that basal blood levels and total plasma clearance of NE during NE infusion are usually normal in essential hypertension. A low threshold of the pressor effect of NE in the presence of normal adrenergic activity may contribute to the development and/or maintenance of essential hypertension.

The total plasma clearance of norepinephrine (NE) was assessed during steady state NE infusion at two different dose rates in 27 patients with non-azotemic diabetes mellitus as compared with 27 normal subjects. Lower NE dose rates were required in diabetics than in normal subjects (P less than 0.001) to induce similar increases in blood pressure. However, plasma NE levels during NE infusion correlated closely (r = 0.79 and 0.78; P less than 0.001) with concomitant dose rates, and this relationship was similar in both study groups. Moreover, the plasma NE clearance did not differ between low and high dose rates of NE infusion, and was similar in diabetics and normal subjects (6.0 +/- 3.1 and 5.1 +/- 2.6 liter/min, respectively). It correlated inversely with the pre-infusion plasma NE (r = -0.38 and -0.53; P less than 0.05);this relationship was also similar in the two groups. The correlation relating plasma NE to NE infusion rates as well as the plasma NE clearance did not differ between the 13 diabetics without and the 14 with signs of peripheral neuropathy or between the 17 patients with normal and the 10 patients with high blood pressure. These findings suggest that the kinetics of circulating NE are usually unaltered in non-azotemic diabetes mellitus. An increased pressor responsiveness to NE, in the presence of normal plasma NE concentrations and clearance rates, may be a setting predisposing for the development of hypertension in diabetic patients.

Interrelations between age and plasma renin, aldosterone and cortisol levels, urinary catecholamiens, plasma and blood volumes, exchangeable body sodium and blood pressure wwere studied in 28 young (19 to 29 years), 16 middle-aged (32 to 58 years) and 15 elderly (60 to 74 years) healthy subjects. Supine and upright plasma renin and supine aldosterone levels decreased while urinary noradrenaline excretion rate increased progressively with aging (r= greater than 0.34; p less than 0.05), with significant differences in mean values between young and elderly subjects (p less than 0.02). There was also an age-related decrease in upright plasma aldosterone concentration, although this was no statistically significant. Furthermore, mean plasma cortisol concentrations increased in response to upright posture in elderly ( + 50%; p less than 0.02), but not in young ( --10%) or middle-aged ( --8%) subjects. Blood pressure correlated with age ( r =0.35; p less than 0.05) or noradrenaline excretion rate ( r= 0.34) in the entire study population and with blood volume in the elderly ( r = 0.68), but not in the young or middle-aged study. Groups. There were no significant age-related differences in the body sodium/volume state, basal plasma cortisol levels or urinary adrenaline excretion rate, and plasma renin or aldosterone levels did not correlate with these parameters or with blood pressure. It is concluded that the influence of age on plasma renin or aldosterone levels, plasma cortisol responsiveness to upright posture, and urinary noradrenaline excretion should be taken into consideration, whenever these factors have to be interpreted in patients with arterial hypertension or other clinical disorders. Further more, these data are conssitent with the possiblity that in normal man increases in supine blood pressure with aging may be related at least partly to concomitant changes in free peripheral noradrenaline.

Two patients with orthostatic hypotension, complicating diabetes mellitus, were treated with dopaminergic antagonist metoclopramide alone or combined with the nonsteroidal anti-inflammatory agent flurbiprofen. Both patients responded favorably to combined treatment of both drugs, with improvement of orthostatic hypotension. In one case, this improvement persisted after withdrawal of flurbiprofen on metoclopramide monotherapy. Blood volume and plasma aldosterone, norepinephrine, and epinephrine levels were unaltered during treatment with these agents. However, plasma renin activity was markedly decreased and, in one patient, exchangeable sodium was increased by 250 mmol. Metoclopramide, alone or combined with the nonsteroidal agent flurbiprofen, may be useful in the treatment of postural hypotension associated with diabetes mellitus. The favorable influence of these agents on blood pressure could not be explained by blood volume expansion or activation of the sympathetic or renin-angiotensin-aldosterone systems.

Treatment with the commonly used diuretic, chlorthalidone, has previously been found to increase the serum low-density-lipoprotein cholesterol (LDL-C) fraction. Therefore, the effects of two new agents, tienilic acid (a combined diuretic-uricosuric) and indapamide on serum lipid and lipoprotein levels were assessed. Six weeks of treatment with tienilic acid, 250 mg/day, markedly decreased serum uric acid and significantly increased LDL-C and triglycerides in 16 men. In contrast, indapamide 2.5 mg/day, had no apparent influence on serum lipids or lipoproteins in 18 men.

The efficacy and side effects of two potent vasodilatators, namely diazoxide and minoxidil given orally, were compared in 11 patients who had hypertension refractory to conventional drug treatment. The latter included diuretics, betablockers and/or sympatholytics, and either dihydralazine or prazosin. In a crossover approach, dihydralazine and prazosin were withdrawn and replaced by diazoxide or minoxidil. In nine patients the diazoxide phase preceded the minoxidil treatment, while in two it followed minoxidil treatment. Before introduction of the more potent vasodilators blood pressure averaged 181/107 mm Hg in the supine and 161/103 mm Hg in the upright position. Both, oral diazoxide (median dose 400 mg/d( and minoxidil (medium dose 17.5 mg/d) produced similar decreases (p < 0.02) in mean arterial pressure (-15%) in the supine and (-11 vs. -12%) in the upright position. They caused a comparable tendency for sodium retention and weight gain which could be satisfactorily controlled with increased diuretic therapy, except in one patient. Hypertrichosis occurred with both drugs, but tended to be somewhat milder with diazoxide. Electrocardiograms remained generally unchanged. Plasma glucose levels were increased during diazoxide treatment in six patients necessitating interruption of this therapy in four patients. It is concluded that the antihypertensive potency and most side effect of orally administered diazoxide are comparable to those of minoxidil, except for diazoxide-related hyperglycemia which may limit the use of this substance.

Quantitative assessment of signs or symptoms of neuropathy, and the beat-to-beat variation, valsalva, orthostasis, handgrip and cold pressor tests, and measurements of plasma renin and catecholamine excretion rate were performed in 23 diabetic patients and 10 age-matched normal subjects. Significant inverse correlations were found between the clinical score and the beat-to-beat variation (a test of efferent vagus function) (r=-0.55, -0.72, P less than 0.0005) or the pressor response to handgrip (possible test of efferent sympathetic integrity (r=p less than 0.005) or the values of both tests combined (r=-0.79, P less than 0.0005); but not with the other measured parameters. Beat-to-beat variation was abnormal in all 9 diabetics with increased and in 9 of 14 with normal clinical score, whereas only seven and one patient from these subgroups, respectively, had an abnormal Valsalva ratio. The pressor response to handgrip was only slightly reduced in the diabetic patients, with greater tendency in those with abnormal clinical score. Additional possible indices of adrenergic dysfunction such as the pressor response to cold stimulus, plasma renin levels and noradrenaline or adrenaline excretion rates did not differ significantly between normal subjects and diabetics. These finding demonstrate a greater prevalence of parasympathetic as compared to sympathetic impairment in diabetic autonomic neuropathy; the beat-to-beat variation was the most sensitive among the tests used. An assessment of clinical evidence combined with non-invasive functional procedures such as the beat-to-beat variation and handgrip tests provide a valuable and easy to perform tool in the evaluation of diabetic neuropathy.

The responsiveness of plasma aldosterone levels to various stimuli was evaluated in 44 normal subjects, 17 patients with mild to moderate renal failure, 30 patients with terminal renal failure, and 13 anephric subjects. Plasma aldosterone, renin activity (PRA), cortisol, sodium, and potassium levels were measured before and after one hour of upright posture (N = 191); ACTH infusions (N = 76); and angiotensin II infusion (N = 36). Plasma aldosterone responses correlated (r greater than or equal to 0.53; p less than 0.02) with basal plasma aldosterone levels during upright posture in all four groups, with ACTH infusion in all groups except anephric subjects, and with angiotensin II administration in patients with mild to moderate renal failure or patients combined. These relationships were consistently closer than those between aldosterone responses and changes in PRA or basal PRA. However, postural aldosterone responsiveness at any given basal aldosterone level was significantly lower in patients with renal disease than in normal subjects, and this was associated with a parallel impairment in renin responsiveness. In contrast, when related to basal levels aldosterone responsiveness to ACTH or angiotensin II appreared to be comparable in normal subjects and patients with renal disease. Aldosterone responses to posture, ACTH, or angiotensin II did not correlate with associated changes in plasma cortisol, sodium, or potassium levels. These data suggest that basal adrenal secretory activity is a major factor conditioning aldosterone responsiveness to various stimuli in normal subjects as well as in patients with renal disease.

Several pressor factors were studied before and during chronic minoxidil therapy (median dose 27.5 mg/day) in 16 patients with hypertension that was refractory to conventional drugs. Following treatment with minoxidil and intensified diuretic therapy, blood pressure was decreased markedly; pulse rate, body weight, plasma volume, plasma aldosterone and epinephrine levels were not significantly altered, while plasma renin activity tended to be increased. Supine and upright plasma norepinephrine concentrations were increased by 140 (P less than 0.005) and 50% (P less than 0.05), respectively, but no significant change in urinary norepinephrine excretion was apparent. The latter parameter may not be a close index of sympathetic activity in patients with severe hypertension treated with minoxidil. While a search for underlying pheochromocytoma is always indicated in refractory hypertension, it appears mandatory to evaluate plasma catecholamines prior to or following discontinuation of treatment with minoxidil, to avoid a wrong diagnosis of pheochromocytoma.

Relationships between plasma norepinephrine (PNE) or epinephrine (PE) and urinary norepinephrine (UNE) or epinephrine (UE) excretion rates were studied in 37 normal subjects, 39 patients with benign essential hypertension, 23 with unilateral renal hypertension, and 20 with bilateral renal disease (serum creatinine 2.3 +/- 2.6 mg/100 ml). measurements were also performed after 6 weeks of diuretic treatment in 27 normal subjects and all patients with essential hypertension. In the untreated state, PNE and UNE values were generally normal in essential or unilateral renal hypertension; PNE tended to be decreased in diabetics and increased in bilateral renal disease. Diuretic treatment caused a tendency for slightly increased PNE and UNE. UNE correlated significantly with supine PNE or upright PNE or their mean value, and this relationship appeared to be comparable between untreated normal subjects and the various patients groups, except for a tendency for slightly higher PNE at given UNE values in bilateral renal disease. No significant correlations between UE and PE were apparent in the normal subjects or patient groups. These data demonstrate a dissociation of UE from PE levels. In contrast, UNE is an approximative index of PNE, and this relationship appeared to be generally unaltered in essential or unilateral renal hypertension. In patients with bilateral renal disease the slight shift of this relationship indicates that consideration of renal function is necessary for interpretation of NE levels.

Plasma catecholamines and renal function were evaluated in 18 patients with essential hypertension treated with the alpha and beta adrenoceptor blocking agent, labetalol. Following 6 weeks of labetalol therapy, blood levels of epinephrine and norepinephrine remained unaltered. Glomerular filtration rate and renal plasma flow were decreased similarly by about 20% (P less than 0.025). Tubular rejection fraction of sodium was increased by 36% (P less than 0.001) while sodium excretion was comparable to control conditions. Labetalol's potential to cause a mild reduction in kidney function should be considered, but may have no clinical consequences in most hypertensive patients receiving such treatment. The lack of increased plasma catecholamine levels during therapy supports the concept that labetalol's alpha-blocking potential is limited to post-junctional receptors, leaving the prejunctional feedback control of catecholamine release intact. Moreover, labetalol's blood pressure-lowering mechanism may be largely independent of changes in sympathetic nervous activity.

Studies in 55 patients with benign essential hypertension showed that the beta-blockers bufuralol (22 patients) and propranolol (33 patients) at a dose ratio of 1:4, possess comparable antihypertensive efficacy despite different properties regarding intrinsic sympathomimetic activity. Beta-blocker-monotherapy normalized blood pressure ( less than 140/90 mm Hg) in one fourth of the patients. Body weight and plasma and blood volumes remained unchanged during beta-blockade of four to six weeks duration, the mean plasma potassium was slightly increased. The inhibition of plasma renin activity (PRA) was more pronounced with propranolol (-69%) than with bufuralol (-47%). Wirth both beta-blockers decreases in blood pressure correlated inversely with pre-treatment PRA (p less than 0.05). Propranolol-induced changes in blood pressure correlated also with associated changes in PRA (p less than 0.005); in contrast, no such relationship was observed with bufuralol. The blood pressure effects of bufuralol, however, correlated significantly with changes in urinary noradrenaline excretion (r=0.41; p less than 0.05). Patient sub-groups with low, normal or high pre-treatment PRA in the average showed a comparable pattern of pre-treatment noradrenaline excretion and patients with normal renin levels exreted more adrenaline than those with low renin levels (p less than 0.001). These data are consistent with the concept that in untreated essential hypertension PRA may be an index of adrenergic activiity, the latter representing an important determinant of blood pressure response to beta-blockade. The blood pressure lowering effects of bufuralol in benign essential hypertension seem to be independent of renin and may be related, at least partly, to diminished free peripheral noradrenaline levels.

In order to study the degree and pathogenic aspects of the secondary hyperlipoproteinemia in patients under diuretic therapy we measured serum lipids, lipoproteins and the apoproteins A1, A2 and B in 12 adults after a 4 weeks placebo period and 6 weeks of treatment with chlorthalidon. There was a significant increase in atherogenic low density lipoproteins (LDL), (18%, P less than 0.05) whereas the high density lipoprotein-cholesterol Apo A1 and A2 levels were not significantly altered. The same was true for the total serum triglyceride- and the very low density lipoprotein- and LDL-triglyceride levels. The activity of lipoprotein lipase and hepatic triglyceride lipase was slightly but not significantly increased. A delayed LDL-catabolism seems to be the most probable pathogenic mechanism underlying the Chlorthalidon-induced hyperlipoproteinemia.

To obtain a comparative assessment of 5 different clinical autonomic function tests as related to age and gender in normal man, the beat-to-beat variation during deep breathing (BBV), orthostatic 30/15 R-R ratio, heart rate response to the Valsalva manoeuvre, blood pressure response to sustained handgrip and orthostatic blood pressure response were evaluated in 120 healthy subjects (60 women and 60 men) aged 22 to 92 yrs. Each of the functional parameters depending on cardiac parasympathetic integrity, i.e. the beat-to-beat variation, orthostatic 30/15 R-R ratio and Valsalva ratio, decreased (P less than 0.0001) progressively with increasing age. The blood pressure response to handgrip, which depends on the efferent sympathetic function, was unchanged, while the orthostatic response of systolic blood pressure, which depends on the function of the entire reflex arch, was augmented only minimally (P less than 0.001) with increasing age. No significant dependence on gender was noted, although blood pressure responses to handgrip tended to be slightly greater in men than women. Beat-to-beat variation expressed as the standard deviation of the mean R-R interval correlated with mean heart rate (P less than 0.05), while the coefficient of variation and the exspiration/inspiration ratio of beat-to-beat variation did not. The orthostatic 30/15 R-R ratio and beat-to-beat variation tended to be more closely interrelated (r = 0.56 to 0.63) than any of these tests with the Valsalva ratio (r = 0.51). The findings indicate that consideration of age may improve the diagnostic value of the orthostatic 30/15 R-R ratio.(ABSTRACT TRUNCATED AT 250 WORDS)