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

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 x 10(-10) M to 1 x 10(-5) M) caused concentration-dependent contraction of the endothelium intact aortic rings. In the presence of hydroxyl radical scavengers, histidine (1 x 10(-3) M), mannitol (3 x 10(-3) M), dimethyl sulfoxide (50 x 10(-3) M) or thiourea (1 x 10(-3) M), 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, in N-G-nitro-L-arginine methyl ester (L-NAME) (1 x 10(-5) M, 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. (C) 1998 The Italian Pharmacological Society.