Vasorelaxing effects of atrial and brain natriuretic peptides on coronary circulation in heart failure

Natriuretic peptide (NP) receptor has been postulated to be downregulated under a high concentration of atrial NP (ANP) in congestive heart failure (CHF), but limited information is available on how the vascular functional responsiveness to NPs is altered in coronary circulation during CHF. We assessed the relaxant effects of ANP, brain NP (BNP), and other vasodilators in isolated coronary arteries obtained from dogs with and without severe CHF induced by rapid right ventricular pacing. In CHF dogs, plasma ANP and cGMP concentrations were elevated compared with control dogs. In CHF arteries the relaxant effects of ANP and BNP (10(-8) and 10(-7) mol/l) were suppressed compared with control arteries. Nitroglycerin, nitric oxide, 8-bromo-cGMP, and beraprost sodium produced similar concentration-response curves in both arteries. The addition of 10(-7) mol/l ANP increased the level of tissue cGMP in control arteries, but not in CHF arteries. We conclude that there was a specific reduction in the relaxant effects of ANP and BNP in isolated coronary arteries in severe CHF dogs, which suggests the possibility of the downregulation of NP receptors coupled to guanylate cyclase.