Search

Objective: The hypothesis that been set forward that use of Renin Angiotensin Aldosterone System (RAAS) inhibitors is associated with COVID-19 severity. We set-up a multicenter Italian collaboration (CORIST Project, ClinicalTrials.gov ID: NCT04318418) to retrospectively investigate the relationship between RAAS inhibitors and COVID-19 in-hospital mortality. We also carried out an updated meta-analysis on the relevant studies. Methods: We analyzed 4,069 unselected patients with laboratory-confirmed SARS-CoV-2 infection and hospitalized in 34 clinical centers in Italy from February 19, 2020 to May 23, 2020. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received angiotensin-converting-enzyme inhibitors (ACE-I) or angiotensin-receptor blockers (ARB) with patients who did not. Articles for the meta-analysis were retrieved until July 13th, 2020 by searching in web-based libraries, and data were combined using the general variance-based method. Results: Out of 4,069 COVID-19 patients, 13.5% and 13.3% received ACE-I or ARB, respectively. Use of neither ACE-I nor ARB was associated with mortality (multivariable hazard ratio (HR) adjusted also for COVID-19 treatments: 0.96, 95% confidence interval 0.77-1.20 and HR=0.89, 0.67-1.19 for ACE-I and ARB, respectively). Findings were similar restricting the analysis to hypertensive (N=2,057) patients (HR=1.00, 0.78-1.26 and HR=0.88, 0.65-1.20) or when ACE-I or ARB were considered as a single group. Results from the meta-analysis (19 studies, 29,057 COVID-19 adult patients, 9,700 with hypertension) confirmed the absence of association. Conclusions: In this observational study and meta-analysis of the literature, ACE-I or ARB use was not associated with severity or in-hospital mortality in COVID-19 patients.

Chronic activation of the renin-angiotensin-aldosterone system (RAAS) promotes and perpetuates the syndromes of congestive heart failure, systemic hypertension, and chronic kidney disease. Excessive circulating and tissue angiotensin II (AngII) and aldosterone levels lead to a pro-fibrotic, -inflammatory, and -hypertrophic milieu that causes remodeling and dysfunction in cardiovascular and renal tissues. Understanding of the role of the RAAS in this abnormal pathologic remodeling has grown over the past few decades and numerous medical therapies aimed at suppressing the RAAS have been developed. Despite this, morbidity from these diseases remains high. Continued investigation into the complexities of the RAAS should help clinicians modulate (suppress or enhance) components of this system and improve quality of life and survival. This review focuses on updates in our understanding of the RAAS and the pathophysiology of AngII and aldosterone excess, reviewing what is known about its suppression in cardiovascular and renal diseases, especially in the cat and dog.

Chronic activation of the renin-angiotensin-aldosterone system (RAAS) promotes and perpetuates the syndromes of congestive heart failure, systemic hypertension, and chronic kidney disease. Excessive circulating and tissue angiotensin II (AngII) and aldosterone levels lead to a pro-fibrotic, -inflammatory, and -hypertrophic milieu that causes remodeling and dysfunction in cardiovascular and renal tissues. Understanding of the role of the RAAS in this abnormal pathologic remodeling has grown over the past few decades and numerous medical therapies aimed at suppressing the RAAS have been developed. Despite this, morbidity from these diseases remains high. Continued investigation into the complexities of the RAAS should help clinicians modulate (suppress or enhance) components of this system and improve quality of life and survival. This review focuses on updates in our understanding of the RAAS and the pathophysiology of AngII and aldosterone excess, reviewing what is known about its suppression in cardiovascular and renal diseases, especially in the cat and dog.

Combinations between an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) and hydrochlorothiazide (HCTZ) are among the recommended treatments for hypertensive patients uncontrolled by monotherapy. Four randomized, double-blind, parallel group studies with a similar design, including 1469 hypertensive patients uncontrolled by a previous monotherapy and with ≥1 cardiovascular risk factor, compared the efficacy of a combination of a sulfhydryl ACE inhibitor (zofenopril at 30 or 60 mg) or an ARB (irbesartan at 150 or 300 mg) plus HCTZ 12.5 mg. The extent of blood pressure (BP)-lowering was assessed in the office and over 24 h. Pleiotropic features of the treatments were evaluated by studying their effect on systemic inflammation, organ damage, arterial stiffness, and metabolic biochemical parameters. Both treatments similarly reduced office and ambulatory BPs after 18–24 weeks. In the ZODIAC study a larger reduction in high sensitivity C reactive protein (hs-CRP) was observed under zofenopril (−0.52 vs. +0.97 mg/dL under irbesartan, p = 0.001), suggesting a potential protective effect against the development of atherosclerosis. In the ZENITH study the rate of carotid plaque regression was significantly larger under zofenopril (32% vs. 16%; p = 0.047). In the diabetic patients of the ZAMES study, no adverse effects of treatments on blood glucose and lipids as well as an improvement of renal function were observed. In patients with isolated systolic hypertension of the ZEUS study, a slight and similar improvement in renal function and small reductions in pulse wave velocity (PWV), augmentation index (AI), and central systolic BP were documented with both treatments. Thus, the fixed combination of zofenopril and HCTZ may have a relevant place in the treatment of high-risk or monotherapy-treated uncontrolled hypertensive patients requiring a more prompt, intensive, and sustained BP red

Combinations between an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) and hydrochlorothiazide (HCTZ) are among the recommended treatments for hypertensive patients uncontrolled by monotherapy. Four randomized, double-blind, parallel group studies with a similar design, including 1469 hypertensive patients uncontrolled by a previous monotherapy and with ≥1 cardiovascular risk factor, compared the efficacy of a combination of a sulfhydryl ACE inhibitor (zofenopril at 30 or 60 mg) or an ARB (irbesartan at 150 or 300 mg) plus HCTZ 12.5 mg. The extent of blood pressure (BP)-lowering was assessed in the office and over 24 h. Pleiotropic features of the treatments were evaluated by studying their effect on systemic inflammation, organ damage, arterial stiffness, and metabolic biochemical parameters. Both treatments similarly reduced office and ambulatory BPs after 18–24 weeks. In the ZODIAC study a larger reduction in high sensitivity C reactive protein (hs-CRP) was observed under zofenopril (−0.52 vs. +0.97 mg/dL under irbesartan, p = 0.001), suggesting a potential protective effect against the development of atherosclerosis. In the ZENITH study the rate of carotid plaque regression was significantly larger under zofenopril (32% vs. 16%; p = 0.047). In the diabetic patients of the ZAMES study, no adverse effects of treatments on blood glucose and lipids as well as an improvement of renal function were observed. In patients with isolated systolic hypertension of the ZEUS study, a slight and similar improvement in renal function and small reductions in pulse wave velocity (PWV), augmentation index (AI), and central systolic BP were documented with both treatments. Thus, the fixed combination of zofenopril and HCTZ may have a relevant place in the treatment of high-risk or monotherapy-treated uncontrolled hypertensive patients requiring a more prompt, intensive, and sustained BP red

Introduction: Left ventricular dysfunction (LVD) is an infrequent but significant side effect of certain molecular-targeted cancer therapies and may lead to treatment modification and impact on disease prognosis. There may be a role for beta blockers (BB), angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) in the prevention of LVD. Areas covered: There are multiple definitions for LVD based on clinical and/or imaging features. Molecular-targeted therapies cause reversible LVD. Therapies with well-reported LVD are inhibitors of human epidermal growth factor 2 (HER2), angiogenesis, Abelson murine leukemia viral oncogene homolog (ABL) and the proteasome. BB, ACEI and ARB seem to have a role in the prevention of LVD associated with anthracyclines. Few trials have investigated the role of BB, ACEI and ARB as primary prevention of LVD in molecular-targeted therapies. Their results are not conclusive but a beneficial role cannot be excluded. Expert opinion: Because of inconclusive data, future interventional studies should not include all treated patients with molecular-targeted therapy, but focus on patients at risk for developing LVD. Another option is to study patients who show early signs of LVD to prevent progression to overt heart failure., SCOPUS: re.j, info:eu-repo/semantics/published

Hypertension is one of the major risk factor able to promote development and progression of several cardiovascular diseases, including left ventricular hypertrophy and dysfunction, myocardial infarction, stroke, and congestive heart failure. Also, it is one of the major driven of high cardiovascular risk profile in patients with metabolic complications, including obesity, metabolic syndrome and diabetes, as well as in those with renal disease. Thus, effective control of hypertension is a key factor for any preventing strategy aimed at reducing the burden of hypertension-related cardiovascular diseases in the clinical practice. Among various regulatory and contra-regulatory systems involved in the pathogenesis of cardiovascular and renal diseases, renin-angiotensin system (RAS) plays a major role. However, despite the identification of renin and the availability of various assays for measuring its plasma activity, the specific pathophysiological role of RAS has not yet fully characterized. In the last years, however, several notions on the RAS have been improved by the results of large, randomized clinical trials, performed in different clinical settings and in different populations treated with RAS inhibiting drugs, including angiotensin converting enzyme (ACE) inhibitors and antagonists of the AT1 receptor for angiotensin II (ARBs). These findings suggest that the RAS should be considered to have a central role in the pathogenesis of different cardiovascular diseases, for both therapeutic and preventive purposes, without having to measure its level of activation in each patient. The present document will discuss the most critical issues of the pathogenesis of different cardiovascular diseases with a specific focus on RAS blocking agents, including ACE inhibitors and ARBs, in the light of the most recent evidence supporting the use of these drugs in the clinical management of hypertension and hypertension-related cardiovascular diseases.

Background: Reducing the excessive accumulation of amyloid β-protein (Aβ) in Alzheimer's disease (AD) is a key objective of most AD therapies. Several studies suggest that pharmacological inhibition of angiotensin-converting enzyme (ACE) or its by-product angiotensin II may delay onset or progression of dementia and it has been suggested that this occurs via regulation of Aβ. Intraneuronal oligomeric accumulation of Aβ is postulated to be one of the earliest pathological events. Thus this study investigated the effect of an ACE-inhibitor, captopril, and two angiotensin II receptor blockers (ARBs), eprosartan and valsartan, on intraneuronal Aβ pathology and oligomeric Aβ levels in a triple transgenic (3xTGAD) mouse model of AD. Methods: Male, adult (3-4 month old) 3xTgAD mice (n=39) were randomly assigned to 4 treatment groups: valsartan (0.17g/l), eprosartan (0.8g/l), captopril (5g/l) or normal drinking water and the drugs given ad libitum for 2 months. Mean arterial blood pressure (MABP) was measured at baseline, at 2 weeks and at 2 months when the mice were sacrificed and the brains hemisected for analysis. One hemisphere was processed for Aβ and amyloid precursor protein (APP) immunohistochemistry and the other for biochemical measurement of oligomeric Aβ and APP. ACE activity was measured in the brain and kidney. Results: MABP was significantly reduced at 2 weeks and 2 months in the ACE-I group (p=0.0006) but was unaltered in the ARB groups compared to vehicle. Neither ACE-I nor ARB treatment altered Aβ and APP immunolabelling or the level of Aβ or APP in brain tissue homogenates. Similarly neither ACE-I nor ARB treatment altered ACE activity in either brain or kidney compared to control tissue. Conclusions: ACE-I or ARB administration over 2 months did not affect APP levels or either intraneuronal Aβ or oligomeric Aβ levels in 3xTGAD mice. While ARBs did not alter MABP, captopril did mediate reductions in MABP in the 3xTGAD mice which appeared to be independent

Objectives: The present study evaluates the effects of a 6-month treatment with an ACE-inhibitor (ie, fosinopril) on serum concentrations of total IGF-1 and IGF binding protein (IGFBP)-3 in older adults at high risk for cardiovascular disease. Design: Data are from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study, a double-blind, crossover, randomized, placebo-controlled trial. Setting: Participants were recruited from the communities of Winston Salem, NC, and Greensboro, NC. Participants: Subjects ≥55 years old with high cardiovascular disease risk profile. Intervention: The intervention consisted of 6-month administration of fosinopril vs. placebo. Measurements: Serum concentrations of total IGF-1 and IGFBP-3 were measured in 100 participants of the TRAIN study at baseline, 6-month and 12-month follow-up visits. Differences in total IGF-1 and IGFBP-3 concentrations were assessed using two-sided paired t-tests. Results: The mean age of participants (47% women) was 66.5 (standard deviation 7.2) years. Serum concentrations of total IGF-1 were significantly higher after 6-month treatment with fosinopril compared to placebo (203.73 ng/mL vs 194.24 ng/mL; p=0.02): After ACE-inhibitor intervention, significantly higher serum IGFBP-3 concentrations compared to controls (4308.81 ng/mL vs 4086.93 ng/mL; p=0.03) were also reported. Conclusions: A six-month treatment with fosinopril increases systemic levels of total IGF-1 and IGFBP-3 in older adults with high cardiovascular risk profile. This may represent a potential biological explanation to the beneficial effects of ACE-inhibition on stroke, ischemic heart disease and insulin resistance. The Journal of Nutrition, Health & Aging©.

type:text, We investigated the effects of several frequently described medication regimens on annual percentage change in bone mineral density (BMD). A longitudinal cohort study (a retrospective analysis) was conducted. Subjects in the Adult Health Study (a prospective cohort study begun in 1958) have been followed through biennial medical examinations in Hiroshima, Japan. Participants were 2,111 subjects (67% women; aged 47-95 years) who were undergoing biennial health examinations from 1994 to 2000. The subjects were examined for the effect of certain drugs on bone mineral change during baseline and one follow-up (4 year later) measurements. Mean annual percentage change in BMD at the femoral neck was -0.38% for men, and -1.14% for women. After adjustment for sex, age, change of weight, alcohol consumption, and smoking status, annual percentage change in BMD decreased by 0.61 % among individuals taking angiotensin converting enzyme (ACE) inhibitors continuously in comparison with individuals who had not taken them (p=0.002): also decreased 0.40% among individuals taking benzodiazepines (BZDs) continuously (p=0.034). Our results suggest that careful consideration should be given to the use of ACE inhibitors and BZDs in a cohort of Japanese elderly.

We investigated the effects of several frequently described medication regimens on annual percentage change in bone mineral density (BMD). A longitudinal cohort study (a retrospective analysis) was conducted. Subjects in the Adult Health Study (a prospective cohort study begun in 1958) have been followed through biennial medical examinations in Hiroshima, Japan. Participants were 2,111 subjects (67% women; aged 47-95 years) who were undergoing biennial health examinations from 1994 to 2000. The subjects were examined for the effect of certain drugs on bone mineral change during baseline and one follow-up (4 year later) measurements. Mean annual percentage change in BMD at the femoral neck was -0.38% for men, and -1.14% for women. After adjustment for sex, age, change of weight, alcohol consumption, and smoking status, annual percentage change in BMD decreased by 0.61 % among individuals taking angiotensin converting enzyme (ACE) inhibitors continuously in comparison with individuals who had not taken them (p=0.002): also decreased 0.40% among individuals taking benzodiazepines (BZDs) continuously (p=0.034). Our results suggest that careful consideration should be given to the use of ACE inhibitors and BZDs in a cohort of Japanese elderly.

La néphropathie aux plantes chinoises (CHN) est une maladie rénale grave qui a été décrite pour la première fois en 1993 chez des patientes ayant suivi un régime amaigrissant à base d’extraits de plantes chinoises (Aristolochia fangchi) contenant des acides aristolochiques (AA). Cette néphropathie se caractérise par une atrophie tubulaire et une fibrose interstitielle aboutissant à l’urémie terminale et se complique fréquemment de cancers des voies urinaires. Au moment d’initier ce travail, il subsistait toujours un large débat quant au rôle étiologique réel des acides aristolochiques dans la genèse de cette maladie. En effet, les gélules à visée amaigrissante contenaient d’autres substances potentiellement néphrotoxiques. Mais surtout, il n’existait aucune preuve expérimentale que les AA pouvaient induire une fibrose rénale interstitielle.Dans la première partie de ce travail, nous démontrons que l’injection par voie sous-cutanée d’AA à la dose de 10 mg/Kg/jour à des rats Wistar mâles en déplétion sodée entraîne l’apparition au 35ème jour d’une atrophie tubulaire, d’une fibrose interstitielle et d’une insuffisance rénale, reproduisant ainsi les anomalies caractéristiques de la CHN. Nous avons ensuite montré que la dexfenfluramine, substance anorexigène à action de type sérotoninergique prise concomitamment par les patientes atteintes de CHN, ne potentialise pas la toxicité rénale des AA. Enfin, la stimulation du système rénine angiotensine (SRA) par la déplétion sodée ou l’inhibition de celui-ci par un traitement pharmacologique ne modifie pas la fibrose interstitielle ni l’insuffisance rénale induite par les AA.En conclusion, nous avons réussi à développer un modèle in vivo de fibrose rénale interstitielle induite par les AA. Dès lors nous avons apporté la preuve expérimentale de l’implication des AA dans le développement de la CHN. Ce modèle a permis de démontrer que les autres éléments potentiellement néphrotoxiques contenues dans la cure d’amaigrissement, Doctorat en sciences médicales, info:eu-repo/semantics/nonPublished

La néphropathie aux plantes chinoises (CHN) est une maladie rénale grave qui a été décrite pour la première fois en 1993 chez des patientes ayant suivi un régime amaigrissant à base d’extraits de plantes chinoises (Aristolochia fangchi) contenant des acides aristolochiques (AA). Cette néphropathie se caractérise par une atrophie tubulaire et une fibrose interstitielle aboutissant à l’urémie terminale et se complique fréquemment de cancers des voies urinaires. Au moment d’initier ce travail, il subsistait toujours un large débat quant au rôle étiologique réel des acides aristolochiques dans la genèse de cette maladie. En effet, les gélules à visée amaigrissante contenaient d’autres substances potentiellement néphrotoxiques. Mais surtout, il n’existait aucune preuve expérimentale que les AA pouvaient induire une fibrose rénale interstitielle.Dans la première partie de ce travail, nous démontrons que l’injection par voie sous-cutanée d’AA à la dose de 10 mg/Kg/jour à des rats Wistar mâles en déplétion sodée entraîne l’apparition au 35ème jour d’une atrophie tubulaire, d’une fibrose interstitielle et d’une insuffisance rénale, reproduisant ainsi les anomalies caractéristiques de la CHN. Nous avons ensuite montré que la dexfenfluramine, substance anorexigène à action de type sérotoninergique prise concomitamment par les patientes atteintes de CHN, ne potentialise pas la toxicité rénale des AA. Enfin, la stimulation du système rénine angiotensine (SRA) par la déplétion sodée ou l’inhibition de celui-ci par un traitement pharmacologique ne modifie pas la fibrose interstitielle ni l’insuffisance rénale induite par les AA.En conclusion, nous avons réussi à développer un modèle in vivo de fibrose rénale interstitielle induite par les AA. Dès lors nous avons apporté la preuve expérimentale de l’implication des AA dans le développement de la CHN. Ce modèle a permis de démontrer que les autres éléments potentiellement néphrotoxiques contenues dans la cure d’amaigrissement, Doctorat en sciences médicales, info:eu-repo/semantics/nonPublished

SCOPUS: cp.j, info:eu-repo/semantics/published

SCOPUS: cp.j, info:eu-repo/semantics/published

Post-transplant erythrocytosis (PTE) is increasingly recognized as a complication of kidney transplantation. In this study we report the effect of the angiotesin-converting enzyme (ACE) inhibitor enalapril on hematocrit (Ht) and erythropoietin in four patients with PTE. Four renal allograft recipients with Ht greater than 51 % were studied. Treatment was initiated with enalapril administered orally at a dose of 2.5 mg/day. All the patients had an increase of hemoglobin (Hb) (17.7 ± 0.64 g/dl), Ht (54.5 ± 1.29 %) and red blood cell count (REC) (584 ± 19.2 × 10⁴/μl). All patients responded to enalapril in 8 weeks with a significant decrease of Hb, Ht, and REC. In one patient, the downward trend was more rapid and sustained, and treatment had to be discontinued to prevent the development of anemia. Serum erythropoietin showed normal in all four patients and remained unchanged during the study, even after discontinuation of enalapril treatment. Serum creatinine remained relatively stable throughout the study. These results suggest that PTE may not be dependent upon circulating erythropoietin and that enalapril treatment may be an effective treatment of PTE without renal dysfunction.

The angiotensin converting enzyme inhibitor perindopril and the diuretic indapamide have been shown to be effective antihypertensive agents in patients with chronic renal failure. A fixed low-dose combination of these two agents has been proposed in the treatment of hypertension. We evaluated this combination in 26 patients with mild to moderate essential hypertension and mild to severe chronic renal failure that did not require dialysis. This was a multicenter, open trial consisting of a 2-week single-blind placebo washout period followed by 12 weeks of active treatment. At week 0, the patients received 2 mg perindopril/0.625 mg indapamide once a day or every other day, with the possibility of dosage adjustment to perindopril 4 mg/indapamide 1.25 mg at week 2, week 4, or week 8. A pharmacokinetic analysis using a population pharmacokinetic approach was performed at week 8. Twenty-three patients completed the 12-week study, at which time 14 patients were receiving 2 mg perindopril/0.625 mg indapamide daily, three were receiving 2 mg perindopril/0.625 mg indapamide every other day, and six perindopril 4 mg/indapamide 1.25 mg. Blood pressure readings (supine) decreased from 170.4 ± 19.2/101.5 ± 6.7 mm Hg before active treatment to 146.5 ± 19.7/86.5 ± 10.6 mm Hg at the end of treatment (P < .0001). Pharmacokinetic analysis showed that for indapamide and perindoprilat (the active metabolite of perindopril) the area under the curve (AUC24) increased with the severity of renal failure. No interaction was noted between the two drugs. Mean serum creatinine and sodium and serum potassium levels remained stable during the study. Impairment of renal function occurred in one patient and was considered unrelated to treatment. We conclude that a fixed low-dose perindopril-indapamide combination as first- line treatment has a good safety/efficacy ratio in hypertensive patients with chronic renal failure., SCOPUS: ar.j, info:eu-repo/semantics/published

The angiotensin converting enzyme inhibitor perindopril and the diuretic indapamide have been shown to be effective antihypertensive agents in patients with chronic renal failure. A fixed low-dose combination of these two agents has been proposed in the treatment of hypertension. We evaluated this combination in 26 patients with mild to moderate essential hypertension and mild to severe chronic renal failure that did not require dialysis. This was a multicenter, open trial consisting of a 2-week single-blind placebo washout period followed by 12 weeks of active treatment. At week 0, the patients received 2 mg perindopril/0.625 mg indapamide once a day or every other day, with the possibility of dosage adjustment to perindopril 4 mg/indapamide 1.25 mg at week 2, week 4, or week 8. A pharmacokinetic analysis using a population pharmacokinetic approach was performed at week 8. Twenty-three patients completed the 12-week study, at which time 14 patients were receiving 2 mg perindopril/0.625 mg indapamide daily, three were receiving 2 mg perindopril/0.625 mg indapamide every other day, and six perindopril 4 mg/indapamide 1.25 mg. Blood pressure readings (supine) decreased from 170.4 ± 19.2/101.5 ± 6.7 mm Hg before active treatment to 146.5 ± 19.7/86.5 ± 10.6 mm Hg at the end of treatment (P < .0001). Pharmacokinetic analysis showed that for indapamide and perindoprilat (the active metabolite of perindopril) the area under the curve (AUC24) increased with the severity of renal failure. No interaction was noted between the two drugs. Mean serum creatinine and sodium and serum potassium levels remained stable during the study. Impairment of renal function occurred in one patient and was considered unrelated to treatment. We conclude that a fixed low-dose perindopril-indapamide combination as first- line treatment has a good safety/efficacy ratio in hypertensive patients with chronic renal failure., SCOPUS: ar.j, info:eu-repo/semantics/published

To determine whether the administration of an angiotensin-converting enzyme inhibitor (ACEI) affects the renal hemodynamic changes and the renal handling of urinary protein excretion in response to a protein meal ingestion, we examined the changes in creatinine clearance (CCr) and urinary albumin excretion rate (AER) in response to the ingestion of a meal of tuna fish before and after the administration of enalapril 2.5 mg/day for one week in 7 healthy male volunteers. Before treatment with enalapril, CCr 0, 1, 2, and 3 (before and 1, 2, and 3 h after protein loading; mean±SD) were 118.8 ± 21.6, 136.8±21.7, 144.9^* ±23.2 and 135.9 ± 15.3 ml/min/1.73 m^2 (^*: p < 0.05 vs CCr 0), respectively. Corresponding values after treatment with enalapril were 124.9 ±21.4, 146.6^* ± 16.3, 139.3^* ± 16.9 and 136.0^* ±22.7 ml/min/1.73 m^2 (^*: p<0.05 vs CCr 0). Mean CCr 0, CCr 2 and individual maximal CCr after protein loading did not show any significant difference before and after enalapril administration (individual maximal CCr: before enalapril 150.3± 13.7 vs after enalapril 153.4±13.6 ml/min/1.73 m^2 , NS). Irrespective of the administration of enalapril, no significant differences were observed in AER values before and after the ingestion of the tuna fish meal. Thus, it might appear that in humans who have normal renal function and are receiving long-term treatment with ACEI, CCr 2 or individual maximal CCr after the ingestion of a tuna fish meal could be used as an index of "renal functional reserve". Furthermore, irrespective of the administration of enalapril, the ingestion of tuna fish meal did not affect the renal handling of urinary albumin excretion.

To determine whether the administration of an angiotensin-converting enzyme inhibitor (ACEI) affects the renal hemodynamic changes and the renal handling of urinary protein excretion in response to a protein meal ingestion, we examined the changes in creatinine clearance (CCr) and urinary albumin excretion rate (AER) in response to the ingestion of a meal of tuna fish before and after the administration of enalapril 2.5 mg/day for one week in 7 healthy male volunteers. Before treatment with enalapril, CCr 0, 1, 2, and 3 (before and 1, 2, and 3 h after protein loading; mean±SD) were 118.8 ± 21.6, 136.8±21.7, 144.9^* ±23.2 and 135.9 ± 15.3 ml/min/1.73 m^2 (^*: p < 0.05 vs CCr 0), respectively. Corresponding values after treatment with enalapril were 124.9 ±21.4, 146.6^* ± 16.3, 139.3^* ± 16.9 and 136.0^* ±22.7 ml/min/1.73 m^2 (^*: p<0.05 vs CCr 0). Mean CCr 0, CCr 2 and individual maximal CCr after protein loading did not show any significant difference before and after enalapril administration (individual maximal CCr: before enalapril 150.3± 13.7 vs after enalapril 153.4±13.6 ml/min/1.73 m^2 , NS). Irrespective of the administration of enalapril, no significant differences were observed in AER values before and after the ingestion of the tuna fish meal. Thus, it might appear that in humans who have normal renal function and are receiving long-term treatment with ACEI, CCr 2 or individual maximal CCr after the ingestion of a tuna fish meal could be used as an index of "renal functional reserve". Furthermore, irrespective of the administration of enalapril, the ingestion of tuna fish meal did not affect the renal handling of urinary albumin excretion., departmental bulletin paper

In the past few years, the combination of two antihypertensive drugs has become a popular approach to hypertension treatment, because this procedure allows one to obtain satisfactory blood pressure control when monotherapy is partially ineffective and also to improve a patient's adherence to the therapeutic regimen, thereby enhancing the tolerance/effectiveness ratio of the treatment. This paper will briefly review the theoretical background and the requirements for an effective combination treatment. It will also discuss the results of the VeraTran Study, a multicenter study performed according to a double-blind parallel group design and aimed at assessing the antihypertensive efficacy of the fixed combination verapamil slow release (SR) and trandolapril, administered for 8 weeks, on clinic and 24-h ambulatory blood pressure. The results of the study demonstrate that the fixed combination of a calcium antagonist and an angiotensin converting enzyme (ACE) inhibitor allows one to obtain an effective and balanced blood pressure control throughout the 24 h.

Aim of the study. To determine parameters of ventilatory function and acid-base balance in patients with chronic heart failure after myocardial infarction and to evaluate effects of perindopril on these parameters. Material and methods. 25 nonsmokers and 15 smokers with NYHA class III-IV heart failure. Ventilatory function (spirometry) and acid-base balance in capillary and venous blood were studied before and after 6 months of therapy with perindopril. Results. Initial parameters of ventilatory function were lower compared to predicted values in both groups but especially in smokers. In nonsmokers treatment with perindopril was associated with significant decrease of vital capacity (by 14,3%, p<0,05) while changes of other parameters of ventilatory function were not significant. In smokers there was a tendency to improvement of bronchial resistance. Initially all patients had compensated respiratory acidosis. Therapy was associated with significant decreases of pCO2 in capillary and venous blood (25,5%, p<0,05, and 18,2%, p<0,05, respectively,) and of capillary to venous blood sO2 ratio (48,3%, p<0,05).

We investigated the effects of several frequently described medication regimens on annual percentage change in bone mineral density (BMD). A longitudinal cohort study (a retrospective analysis) was conducted. Subjects in the Adult Health Study (a prospective cohort study begun in 1958) have been followed through biennial medical examinations in Hiroshima, Japan. Participants were 2,111 subjects (67% women; aged 47-95 years) who were undergoing biennial health examinations from 1994 to 2000. The subjects were examined for the effect of certain drugs on bone mineral change during baseline and one follow-up (4 year later) measurements. Mean annual percentage change in BMD at the femoral neck was -0.38% for men, and -1.14% for women. After adjustment for sex, age, change of weight, alcohol consumption, and smoking status, annual percentage change in BMD decreased by 0.61 % among individuals taking angiotensin converting enzyme (ACE) inhibitors continuously in comparison with individuals who had not taken them (p=0.002): also decreased 0.40% among individuals taking benzodiazepines (BZDs) continuously (p=0.034). Our results suggest that careful consideration should be given to the use of ACE inhibitors and BZDs in a cohort of Japanese elderly.