L-NAME enhances responses to atrial natriuretic peptide in the pulmonary vascular bed of the cat

This study investigated the hypothesis that atrial natriuretic peptide (ANP ) responses are mediated by particulate guanylate cyclase in the pulmonary vascular bed of the cat. When tone in the pulmonary vascular bed was raised to a high steady level with the thromboxane mimic U-46619, injections of A NP caused dose-related decreases in lobar arterial pressure. After administ ration of HS-142-1, an ANP-A- and ANP-B-receptor antagonist, vasodilator re sponses to ANP were reduced. The nitric oxide (NO) synthase inhibitor N-ome ga-nitro-L-arginine methyl ester (L-NAME) enhanced ANP vasodilator response s, suggesting that inhibition of NO modulates ANP responses. L-NAME adminis tration with constant 8-bromo-cGMP infusion attenuated the increased vasodi lator response to ANP, suggesting that supersensitivity to ANP occurs upstr eam to activation of a cGMP-dependent protein kinase. In pulmonary arterial rings, ANP produced concentration-related vasorelaxant responses with and without endothelium. Methylene blue, L-NAME, or N-omega-monomethyl-L-argini ne did not alter ANP vasorelaxant responses. These data show that ANP super sensitivity observed in the intact pulmonary vascular bed is not seen in is olated pulmonary arterial segments, suggesting that it may only occur in re sistance vessel elements. These results suggest that ANP responses occur th rough activation of ANP-A and/or -B receptors in an endothelium-independent manner and are modulated by NO in resistance vessel elements in the pulmon ary vascular bed of the cat.