Involvement of reactive oxygen species in angiotensin II-induced vasoconstriction.
In recent years it has been shown that angiotensin II (Ang II) stimulates formation of reactive oxygen species (ROS), presumably by activation of NAD(P)H oxidase. This ROS formation has been primarily associated with cellular growth regulation by Ang II. The objective of the present study was to investigate whether these ROS contribute to Ang II-induced vasoconstriction. Experiments were performed in isolated rat thoracic aorta. Concentration response curves were constructed for Ang II in the absence and presence of the NAD(P)H oxidase inhibitor DPI, and ROS scavengers catalase and EUK-8. Inhibition of NAD(P)H oxidase as well as scavenging of ROS, decreased the contractile response to Ang II. Administration of NADPH, a substrate for NAD(P)H oxidase, produced vasoconstriction that proved to be sensitive for DPI, catalase, and EUK-8. Exposure of the vessels to exogenous ROS, induced by electrolysis of the organ bath medium, also resulted in a contractile response that was decreased by ROS scavenging. The results suggest that ROS play a role in Ang II-induced vasoconstriction via the activation of NAD(P)H oxidase.
de Groot
Annemieke A
AA
Department of Pharmacorherapy, Academic Medical Cener, University of Amsterdam, The Netherlands. a.a.degroot@amc.uva.nl
van Zwieten
Pieter A
PA
Peters
Stephan L M
SL
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic; D002374:Catalase / Q000378:metabolism; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D017382:Reactive Oxygen Species; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D002374:Catalase; D020928:Mitogen-Activated Protein Kinases