Effects of ramipril on renal function during progressive overpacing-induced heart failure in dogs

Myrielle Mathieu Laboratory of Physiology, Faculty of Medicine, Free University of Brussels, Route de Lennik 808, CPI 604, 1070 Brussels, Belgium

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Sophie Motte Laboratory of Physiology, Faculty of Medicine, Free University of Brussels, Route de Lennik 808, CPI 604, 1070 Brussels, Belgium

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 DVM
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Lynn Ray Laboratory of Physiology, Faculty of Medicine, Free University of Brussels, Route de Lennik 808, CPI 604, 1070 Brussels, Belgium

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Anne Pensis Laboratory of Physiology, Faculty of Medicine, Free University of Brussels, Route de Lennik 808, CPI 604, 1070 Brussels, Belgium

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Pascale Jespers Laboratory of Physiology, Faculty of Medicine, Free University of Brussels, Route de Lennik 808, CPI 604, 1070 Brussels, Belgium

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Serge Brimioulle Laboratory of Physiology, Faculty of Medicine, Free University of Brussels, Route de Lennik 808, CPI 604, 1070 Brussels, Belgium

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Valérie Laroute Unité Mixte de Recherche 181 Physiopathologie et Toxicologie Experimentales, Institut National de la Recherche Agronomique, Ecole Nationale Vétérinaire de Toulouse, 23 Chemin des Capelles, BP 87614, 31076 Toulouse Cedex 3, France

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Robert Naeije Laboratory of Physiology, Faculty of Medicine, Free University of Brussels, Route de Lennik 808, CPI 604, 1070 Brussels, Belgium

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Kathleen Mc Entee Laboratory of Physiology, Faculty of Medicine, Free University of Brussels, Route de Lennik 808, CPI 604, 1070 Brussels, Belgium

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Abstract

Objective—To investigate the effects of preventive angiotensin converting enzyme inhibitor treatment with ramipril in dogs with progressively severe experimentally induced heart failure.

Animals—20 dogs.

Procedures—Dogs were randomly allocated to receive no treatment (control) or ramipril (0.125 mg/kg, PO, daily) for 7 weeks. Physical examination, repetitive catheterization of the right side of the heart, and echocardiography were performed before the study (day 0) and weekly for 7 weeks. Renal plasma flow (RPF) as determined by para-aminohippuric acid clearance and glomerular filtration rate (GFR) as determined by creatinine and iohexol clearances were measured on day 0 and at weeks 4 and 7.

Results—Overpacing induced a progressive increase in right atrial pressure (RAP) and pulmonary artery pressure, occluded (PAPO), with a decrease in systemic arterial pressure. There were progressive alterations of echocardiographic indices of diastolic and systolic ventricular function. The RPF and GFR decreased before cardiac output decreased, and filtration fraction increased. The logarithm of the urinary sodium–to–potassium concentration ratio (log10[Na+/K+]) decreased. Significant effects of ramipril included a delay in clinical signs of heart failure, a late decrease in RAP and PAPO, and increases in the sodium excretion fraction and log10(Na+/K+). There was a satisfactory agreement between the creatinine and iohexol clearance measurements.

Conclusions and Clinical Relevance—Results suggest that, in this rapid-evolving, dilated cardiomyopathy, activation of the renin-angiotensin system contributes to the pathophysiology of heart failure late in the disease and essentially by an activation of renal salt and water retention.

Abstract

Objective—To investigate the effects of preventive angiotensin converting enzyme inhibitor treatment with ramipril in dogs with progressively severe experimentally induced heart failure.

Animals—20 dogs.

Procedures—Dogs were randomly allocated to receive no treatment (control) or ramipril (0.125 mg/kg, PO, daily) for 7 weeks. Physical examination, repetitive catheterization of the right side of the heart, and echocardiography were performed before the study (day 0) and weekly for 7 weeks. Renal plasma flow (RPF) as determined by para-aminohippuric acid clearance and glomerular filtration rate (GFR) as determined by creatinine and iohexol clearances were measured on day 0 and at weeks 4 and 7.

Results—Overpacing induced a progressive increase in right atrial pressure (RAP) and pulmonary artery pressure, occluded (PAPO), with a decrease in systemic arterial pressure. There were progressive alterations of echocardiographic indices of diastolic and systolic ventricular function. The RPF and GFR decreased before cardiac output decreased, and filtration fraction increased. The logarithm of the urinary sodium–to–potassium concentration ratio (log10[Na+/K+]) decreased. Significant effects of ramipril included a delay in clinical signs of heart failure, a late decrease in RAP and PAPO, and increases in the sodium excretion fraction and log10(Na+/K+). There was a satisfactory agreement between the creatinine and iohexol clearance measurements.

Conclusions and Clinical Relevance—Results suggest that, in this rapid-evolving, dilated cardiomyopathy, activation of the renin-angiotensin system contributes to the pathophysiology of heart failure late in the disease and essentially by an activation of renal salt and water retention.

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