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(Circulation. 1997;96:3655-3664.)
© 1997 American Heart Association, Inc.

Articles

Impaired Nitric Oxide–Mediated Renal Vasodilation in Rats With Experimental Heart Failure

Role of Angiotensin II

Zaid A. Abassi, PhD; Konstantin Gurbanov, MD; Susan E. Mulroney, PhD; Clariss Potlog, MD; Terry J. Opgenorth, PhD; Aaron Hoffman, MD; Aviad Haramati, PhD; ; Joseph Winaver, MD

From the Department of Physiology and Biophysics, Faculty of Medicine, Technion, Haifa, Israel (Z.A.A., K.G., C.P., A. Hoffman, J.W.); Cardiovascular Pharmacology, Abbott Laboratories, Abbott Park, Ill (T.J.O.); and Department of Physiology and Biophysics, Georgetown University School of Medicine, Washington, DC (S.E.M., A. Haramati).

Correspondence to Aviad Haramati, PhD, Department of Physiology and Biophysics, Georgetown University School of Medicine, Room 249 Basic Sciences Bldg, 3900 Reservoir Rd NW, Washington, DC 20007.

Background Congestive heart failure (CHF) is associated with a decrease in renal perfusion. Because endothelium-derived NO is important in the 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 performed in rats with experimental high-output CHF induced by aortocaval (AV) fistula and sham-operated controls. In controls, incremental doses of acetylcholine (ACh, 1 to 100 µg · 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 attenuated 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 -independent renal vasodilators in CHF rats occurred despite a normal baseline and stimulated NO₂+NO₃ excretion and normal expression of renal endothelial NO synthase (eNOS), as determined by eNOS mRNA levels and immunoreactive protein. Infusion of the NO precursor L-arginine did not affect baseline RBF or the response to ACh in rats with CHF. However, administration of the nonpeptide angiotensin II receptor antagonist A81988 before ACh completely restored the renal vasodilatory response to ACh in CHF rats.

Conclusions This study demonstrates that despite a significant attenuation in the NO-related renal vasodilatory responses, the integrity of the renal NO system is preserved in rats with chronic AV fistula. This impairment in NO-mediated renal vasodilation in experimental CHF appears to be related to increased activity of the renin-angiotensin system and may contribute further to the decrease in renal perfusion seen in CHF.

Key Words: fistula • kidney • endothelium-derived factors • acetylcholine • hemodynamics

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