Relaxant effect of C-type natriuretic peptide involves endothelium and nitric oxide-cGMP system in rat coronary microvasculature

Objective: Recent evidence suggests a possible role for nitric oxide (NO) i n atrial natriuretic peptide-induced blood pressure effects. We tested the hypothesis that C-type natriuretic peptide (CNP)-mediated relaxation of the rat coronary circulation involves NO and activation of soluble guanylyl cy clase. Methods: Rat hearts (n=6 per group) were perfused in vitro at consta nt flow and the effect of CNP (0.1-3 mu mol/l) on coronary perfusion pressu re (a measure of vascular tone) and release of guanosine 3 ' ,5 ' -cyclic m onophosphate (cGMP) was determined in absence and presence of the nitric ox ide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA; 0.2 mmol/l) or the natriuretic peptide receptor antagonist HS-142-1 (50 mug/ml). The involveme nt of Ca2+-gated and ATP-dependent K+ channels in CNP-induced relaxation wa s tested with iberiotoxin (30 nmol/l) and glibenclamide (1 mu mol/l), respe ctively. Rings of rat aorta (n=12) were tested using the organ bath set-up. Results: CNP reduced perfusion pressure from 134 +/-2 mmg (baseline) to 71 +/-1 mmHg (-48%) and this effect was significantly attenuated by L-NNA (-3 7%) or HS-142-1 (-19%). In presence of glibenclamide, CNP reduced perfusion pressure to 92 +/-2 mmHg (-32%), in presence of iberiotoxin to 93 +/-1 mmH g (-30% and in their combined presence to 102 +/-2 mmHg (-23%) (P <0.05 vs. corresponding control). Basal release of cGMP was increased up to 4-fold b y CNP and this increase was reduced (-50%) in presence Of L-NNA or HS-142-1 (-68%). By contrast, relaxation of rat aortic rings mounted in organ baths was insensitive to inhibition by L-NNA. Conclusion: Relaxation of the coro nary resistance vessels of the rat by CNP is partly mediated by the NO-cGMP pathway. These novel data support the existence of an endogenous link betw een soluble and particulate guanylyl cyclases in the control of natriuretic peptide-mediated coronary resistance vessel function. (C) 2001 Elsevier Sc ience BY All rights reserved.