Peroxynitrite relaxes canine coronary arteries in both hypoxia and reperfusion

Peroxynitrite (ONO₂) is a noxious metabolite of nitric oxide previously shown to relax arteries during normoxia; however the vascular effects of ONO₂ during hypoxia or reperfusion have not been examined. We investigated the influence of ONO₂ on canine coronary arteries suspended in organ chambers during normoxia (5%CO₂/95%O₂), hypoxia (5%CO₂/95%N₂) and after a 15min hypoxic insult. Arteries were stretched to optimal length-tension and prostaglandin F_2α (2×10^-6M) contracted Vessels maintained at normoxia relaxed completely to ONO₂ (10^-9-10^-5M, n=5), and similar ONO₂-induced relaxations occurred in endothelial-denuded arteries (n=4). Arteries exposed to hypoxia after precontraction also relaxed in a similar fashion (n=5, P=NS, ANOVA). Arteries were exposed to a hypoxic insult for 15min, reoxygenated for 15min, and then contracted. Relaxation to ONO₂ was similar to controls maintained in normoxia for the same period of time (n=4). Methylene blue was added prior to ONO₂ dose-response curves in paired experiments. Mild attenuation of the relaxation was noted in all groups (n=4, P=NS). This study demonstrates peroxynitrite-induced relaxations during normoxia, hypoxia, or after a 15min hypoxic insult which are not altered by inhibition of soluble guanylate cyclase.