Role of endothelial-derived reactive oxygen species and nitric oxide in norepinephrine-induced rat aortic ring contractions

Abstract

In the present investigation involvement of endothelial-derived reactive oxygen species (ROS) and their interaction with nitric oxide (NO), during norepinephrine (NE)-induced contraction of rat aortic rings was studied. NE (1× 10^-10M to 1× 10^-5M ) caused concentration-dependent contractio n of the endothelium intact aortic rings. In the presence of hydroxyl radical scavengers, histidine (1× 10^-3M ), mannitol (3 × 10^-3M ), dimethyl sulfoxide (50 × 10^-3M ) or thiourea (1 × 10^-3M ), superoxide dismutase (superoxide radical scavenger, SOD 10 or 100 U ml^-1) or catalase (hydrogen peroxide inactivator 3, 10, or 100 U ml^-1) the concentration-response curve of NE was shifted towards the right. Interestingly, inN^G-nitro-L-arginine methyl ester ( L-NAME) (1 × 10^-5M , a NO synthase inhibitor) pretreated rings, NE-induced contractions were not inhibited by SOD or extracellular hydroxyl radical scavengers (mannitol and histidine). However, in these rings NE-induced contractions were found to be attenuated by endogenous hydroxyl radical scavengers (thiourea and DMSO) or catalase. In the endothelium denuded rings no significant effect of these scavengers on NE-induced contractions was observed. These results thus indicate the involvement of endothelium-derived hydrogen peroxide, superoxide and hydroxyl radicals in the NE-induced contractions. In addition, endothelial NO interacts with the ROS generated during rat aortic ring contractions.