Effects of ramipril on renal function during progressive overpacing-induced heart failure in dogs.
OBJECTIVE
To investigate the effects of preventive angiotensin converting enzyme inhibitor treatment with ramipril in dogs with progressively severe experimentally induced heart failure.


METHODS
20 dogs.


METHODS
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 (log(10)[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 log(10)(Na(+)/K(+)). There was a satisfactory agreement between the creatinine and iohexol clearance measurements.


CONCLUSIONS
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.
Mathieu
Myrielle
M
Laboratory of Physiology, Faculty of Medicine, Free University of Brussels, Belgium.
Motte
Sophie
S
Ray
Lynn
L
Pensis
Anne
A
Jespers
Pascale
P
Brimioulle
Serge
S
Laroute
Valérie
V
Naeije
Robert
R
Mc Entee
Kathleen
K
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D006333:Heart Failure / Q000662:veterinary*; D008297:Male; D017257:Ramipril / Q000627:therapeutic use*; D012079:Renal Circulation / Q000187:drug effects*; D017595:Renal Plasma Flow / Q000187:drug effects*; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D017257:Ramipril