Inhibition of guanylate cyclase stimulation by NO and bovine arterial relaxation to peroxynitrite and H2O2.
The inhibitor of soluble guanylate cyclase (sGC) stimulation by nitric oxide (NO), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), was examined for its effects on the prolonged relaxation of endothelium-removed bovine coronary (BCA) and pulmonary (BPA) arteries to peroxynitrite (ONOO-) and on H2O2-elicited relaxation and sGC stimulation. Our previous studies suggest that ONOO- causes a prolonged relaxation of BPA by regenerating NO and that a 2-min exposure of BCA or BPA to 50 nM NO causes an ONOO--elicited relaxation. The relaxation of K+-precontracted BCA to 50 nM NO or 100 microM ONOO- was essentially eliminated by 10 microM ODQ. ODQ also eliminated relaxation to 0.1 nM-10 microM of NO donor S-nitroso-N-acetyl-penicillamine (SNAP), but it did not alter relaxation to 1-300 microM H2O2. Similar responses were also observed in BPA. ODQ did not increase lucigenin-detectable superoxide production in BCA, and it did not alter luminol-detectable endogenous ONOO- formation observed during a 2-min exposure of BCA to 50 nM NO. In addition, ODQ did not affect tissue release of NO after 2 min exposure of BCA to 50 nM NO. The activity of sGC in BPA homogenate that is stimulated by endogenous H2O2 was not altered by ODQ, whereas sGC activity in the presence of 10 microM SNAP (+fungal catalase) was reduced by ODQ. Thus relaxation of K+-precontracted BCA and BPA to ONOO- appears to be completely mediated by NO stimulation of sGC, whereas the actions of ODQ suggest that NO is not involved in H2O2-elicited relaxation and sGC stimulation. This study did not detect evidence for the participation of additional mechanisms potentially activated by ONOO- in the responses studied.
Iesaki
T
T
Department of Physiology, New York Medical College, Valhalla, New York 10595, USA.
Gupte
S A
SA
Kaminski
P M
PM
Wolin
M S
MS
D000818:Animals; D002417:Cattle; D003331:Coronary Vessels / Q000502:physiology; D006162:Guanylate Cyclase / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009566:Nitrates / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D016877:Oxidants / Q000494:pharmacology; D011651:Pulmonary Artery / Q000502:physiology
D009566:Nitrates; D016877:Oxidants; C039642:peroxynitric acid; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D006162:Guanylate Cyclase