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

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Abstract

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 μmol/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 μg/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 μmol/l), respectively. Rings of rat aorta (n = 12) were tested using the organ bath set-up. Results: CNP reduced perfusion pressure from 134 ± 2 mmHg (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. © 2001 Elsevier Science B.V. All rights reserved.

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Brunner, F., & Wölkart, G. (2001). Relaxant effect of C-type natriuretic peptide involves endothelium and nitric oxide-cGMP system in rat coronary microvasculature. Cardiovascular Research, 51(3), 577–584. https://doi.org/10.1016/S0008-6363(01)00283-8

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