IMPAIRED NITRIC OXIDE-MEDIATED RENAL VASODILATION IN RATS WITH EXPERIMENTAL HEART-FAILURE - ROLE OF ANGIOTENSIN-II

Background Congestive heart failure (CHF) is associated with a decreas e in renal perfusion. Because endothelium-derived NO is important in t he regulation of renal blood flow (RBF), we tested the hypothesis that an impairment in the NO system may contribute to the decrease in RBF in rats with experimental CHF. Methods and Results Studies were perfor med in rats with experimental high-output CHF induced by aortocaval (A V) fistula and sham-operated controls. In controls, incremental doses of acetylcholine (ACh, 1 to 100 mu g . kg(-1) . min(-1)) increased RBF and caused a dose-related decrease in renal vascular resistance (RVR) . However, the increase in RBF and decrease in RVR were markedly atten uated in rats with CHF. Likewise, the effects of ACh on urinary sodium and cGMP excretion were also diminished in CHF rats, as was the renal vasodilatory effect of the NO donor S-nitroso-N-acetylpenicillamine ( SNAP). These attenuated responses to endothelium-dependent and -indepe ndent renal vasodilators in CHF rats occurred despite a normal baselin e and stimulated NO2+NO3 excretion and normal expression of renal endo thelial NO synthase (eNOS), as determined by eNOS mRNA levels and immu noreactive protein. Infusion of the NO precursor L-arginine did not af fect baseline RBF or the response to ACh in rats with CHF. However, ad ministration of the nonpeptide angiotensin LI receptor antagonist A819 88 before ACh completely restored the renal vasodilatory response to A Ch in CHF rats. Conclusions This study demonstrates that despite a sig nificant attenuation in the NO-related renal vasodilatory responses, t he integrity of the renal NO system is preserved in rats with chronic AV fistula. This impairment in NO-mediated renal vasodilation in exper imental CHF appears to be related to increased activity of the renin-a ngiotensin system and may contribute further to the decrease in renal perfusion seen in CHF.