ROLE OF ENDOTHELIAL-DERIVED REACTIVE OXYGEN SPECIES AND NITRIC OXIDE IN NOREPINEPHRINE-INDUCED RAT AORTIC RING CONTRACTIONS

• Published in: Pharmacological research Vol. 38; no. 4; pp. 265 - 274
• Main Authors: SRIVASTAVA, P, HEGDE, L.G, PATNAIK, G.K, DIKSHIT, M
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-10-1998
• Subjects: Animals; Aorta, Thoracic - drug effects; Aorta, Thoracic - physiology; aortic ring contractions, noradrenaline, endogenous reactive oxygen species, endothelium, nitric oxide; Catalase - pharmacology; Dose-Response Relationship, Drug; Endothelium, Vascular - metabolism; Free Radical Scavengers - pharmacology; In Vitro Techniques; Male; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide - physiology; Norepinephrine - pharmacology; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - physiology; Superoxide Dismutase - pharmacology; Vasoconstriction - drug effects; Vasoconstrictor Agents - pharmacology; aortic ring contractions, noradrenaline, endogenous reactive oxygen species, endothelium, nitric oxide
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1006/phrs.1998.0357

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 (1×10−10mto 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, inNG-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.