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) 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.


CONCLUSIONS
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.
Brunner
F
F
Institut für Pharmakologie und Toxikologie, Karl-Franzens-Universität Graz, Universitätsplatz 2, A-8010, Graz, Austria. friedrich.brunner@kfunigraz.ac.at
Wölkart
G
G
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009924:Organ Culture Techniques; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D015221:Potassium Channels; D020098:Natriuretic Peptide, C-Type; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP