C-type natriuretic peptide reduced coronary perfusion pressure by 48%, an effect significantly attenuated by nitric oxide synthase inhibition, indicating partial mediation by the NO-cGMP pathway.
CNP-mediated relaxation of rat coronary resistance vessels is partly mediated by the NO-cGMP pathway, supporting an endogenous link between soluble and particulate guanylyl cyclases.
Absolute Event Rate: 71% vs 134%
p-value: p=<0.05
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 micromol/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 N(G)-nitro-L-arginine (L-NNA; 0.2 mmol/l) or the natriuretic peptide receptor antagonist HS-142-1 (50 microg/ml). The involvement of Ca(2+)-gated and ATP-dependent K(+) channels in CNP-induced relaxation was tested with iberiotoxin (30 nmol/l) and glibenclamide (1 micromol/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.
Friedrich Brünner (Wed,) conducted a other in Coronary microvasculature relaxation. C-type natriuretic peptide (CNP) vs. Baseline / Control was evaluated on Coronary perfusion pressure (p=<0.05). C-type natriuretic peptide reduced coronary perfusion pressure by 48%, an effect significantly attenuated by nitric oxide synthase inhibition, indicating partial mediation by the NO-cGMP pathway.