Effects of Eprosartan on Renal Function and Cardiac Hypertrophy in Rats With Experimental Heart Failure

Abstract

Abstract-Activation of the renin-angiotensin system may contribute to the derangement in renal and cardiac function in congestive heart failure. The present study evaluated the effects of eprosartan, a selective angiotensin II receptor antagonist, on renal hemodynamic and excretory parameters and on the development of cardiac hypertrophy in rats with aortocaval fistula, an experimental model of congestive heart failure. Infusion of eprosartan (1.0 mg/kg) in rats with aortocaval fistula produced a significant increase (ϩ34%) in total renal blood flow and a sustained decrease (Ϫ33%) in the calculated renal vascular resistance. These effects on renal hemodynamics were more pronounced than those observed in sham-operated control rats and occurred despite a significant fall (Ϫ12%) in mean arterial blood pressure. Moreover, eprosartan caused a preferential increase in renal cortical blood perfusion and significantly increased glomerular filtration in rats with congestive heart failure. Chronic administration of eprosartan (5.0 mg/kg per day for 7 days through osmotic minipumps inserted intraperitoneally on the day of operation) resulted in a significant enhancement of urinary sodium excretion compared with nontreated rats with heart failure. Moreover, administration of eprosartan to salt-retaining rats with congestive heart failure resulted in a progressive increase and ultimate recovery in urinary sodium excretion. Finally, early treatment with eprosartan blocked the development of cardiac hypertrophy in rats with aortocaval fistula to a larger extent than the angiotensin-converting enzyme inhibitor enalapril. These findings emphasize the importance of angiotensin II in mediating the impairment in renal function and induction of cardiac hypertrophy in heart failure and further suggest that angiotensin II receptor blockade may be a useful treatment of these consequences in severe cardiac failure. (Hypertension. 1998;32:746-752.)

Evaluation of Atrial Natriuretic Peptide and Brain Natriuretic Peptide in Atrial Granules of Rats with Experimental Congestive Heart Failure

“…A variety of neurohormonal systems are activated in CHF (Pettersson et al 1989;Brodsky et al 1998). These include the vasoconstrictor and antinatriuretic systems, such as the sympathetic nervous system and the renin-angiotensin-aldosterone axis, as well as the upregulation of the natriuretic peptides, as delineated by the high synthesis and release of ANP and BNP (Moe et al 1993).…”

Cardiac and renal effects of omapatrilat, a vasopeptidase inhibitor, in rats with experimental congestive heart failure

“…An ACF was surgically created between the abdominal aorta and inferior vena cava according to the method originally described by Stumpe et al (31) and adapted in our laboratory (1,2,7,37). Briefly, a midline abdominal incision was performed under pentobarbital sodium (Nembutal) anesthesia to expose the vena cava and abdominal aorta distal to the origin of the renal arteries.…”

“…Clinical and experimental data provide strong evidence that this axis is involved in the pathogenesis of the cardiac, renal, and vascular changes of CHF and hypertension (2,4,7,12,14,35,37). Moreover, inhibitors of angiotensin-converting enzyme (ACE) have been found to be highly beneficial in the treatment of patients with CHF (2, 4, 31a, 31b, 37).…”

“…However, the natriuretic and vasodilatory actions of NPs are significantly attenuated in CHF, particularly in advanced stages of the disease (2,37). Angiotensin II has been implicated in the attenuated responsiveness to NPs (2,7,37). Besides clearance receptors (NPR-C), NPs are removed by neutral endopeptidase 24.11 (NEP), a ubiquitous enzyme found in the vasculature, kidney, and heart (6,8).…”

“…Previous studies from our laboratory have shown that the experimental model of rats with an aortocaval fistula (ACF) closely mimics the neurohumoral, renal, and cardiac manifestations of patients with severe CHF (2,7,37). These include a marked degree of cardiac hypertrophy and dilatation, increased activity of the vasoconstrictor RAAS and sympathetic nervous system as well as the NPs system, and a marked decrease in renal perfusion with sodium retention by the kidney (4,12,14,35,37).…”