Journal
CARDIOVASCULAR RESEARCH
Volume 51, Issue 3, Pages 577-584Publisher
OXFORD UNIV PRESS
DOI: 10.1016/S0008-6363(01)00283-8
Keywords
blood pressure; coronary circulation; K-ATP channel; natriuretic peptide; nitric oxide; endothelial function; endothelial receptors
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Objective: Recent evidence suggests a possible role for nitric oxide (NO) in 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 cyclase. Methods: Rat hearts (n=6 per group) were perfused in vitro at constant flow and the effect of CNP (0.1-3 mu mol/l) on coronary perfusion pressure (a measure of vascular tone) and release of guanosine 3 ' ,5 ' -cyclic monophosphate (cGMP) was determined in absence and presence of the nitric oxide (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 involvement of Ca2+-gated and ATP-dependent K+ channels in CNP-induced relaxation was tested with iberiotoxin (30 nmol/l) and glibenclamide (1 mu mol/l), respectively. 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 (-37%) 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 mmHg (-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 by 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 coronary 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 between soluble and particulate guanylyl cyclases in the control of natriuretic peptide-mediated coronary resistance vessel function. (C) 2001 Elsevier Science BY All rights reserved.
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