Faculty Collaboration Database

Role of superoxide and thromboxane receptors in acute angiotensin II-induced vasoconstriction of rabbit vessels. Am J Physiol Heart Circ Physiol 2011 Jun;300(6):H2064-71

Date

04/05/2011

Pubmed ID

21460202

Pubmed Central ID

PMC3119100

DOI

10.1152/ajpheart.01135.2010

Scopus ID

2-s2.0-79958028562 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

This study explored the hypothesis that a portion of angiotensin II-induced contractions is dependent on superoxide generation and release of a previously unidentified arachidonic acid metabolite that activates vascular smooth muscle thromboxane receptors. Treatment of rabbit aorta or mesentery artery with the thromboxane receptor antagonist SQ29548 (10 μM) reduced angiotensin II-induced contractions (maximal contraction in aorta; control vs. SQ29548: 134 ± 16 vs. 93 ± 10%). A subset of rabbits deficient in vascular thromboxane receptors also displayed decreased contractions to angiotensin II. The superoxide dismutase mimetic Tiron (30 mM) attenuated angiotensin II-induced contractions only in rabbits with functional vascular thromboxane receptors (maximal contraction in aorta; control vs. Tiron: 105 ± 5 vs. 69 ± 11%). Removal of the endothelium or treatment with a nitric oxide synthase inhibitor, nitro-l-arginine (30 μM) did not alter angiotensin II-induced contractions. Tiron and SQ29548 decreased angiotensin II-induced contractions in the denuded aortas by a similar percentage as that observed in intact vessels. The cyclooxygenase inhibitor indomethacin (10 μM) or thromboxane synthase inhibitor dazoxiben (10 μM) had no effect on angiotensin II-induced contractions indicating that the vasoconstrictor was not thromboxane. Angiotensin II increased the formation of a 15-series isoprostane. Isoprostanes are free radical-derived products of arachidonic acid. The unidentified isoprostane increased when vessels were incubated with the superoxide-generating system xanthine/xanthine oxidase. Pretreatment of rabbit aorta with the isoprostane isolated from aortic incubations enhanced angiotensin II-induced contractions. Results suggest the factor activating thromboxane receptors and contributing to angiotensin II vasoconstriction involves the superoxide-mediated generation of a 15-series isoprostane.

Author List

Pfister SL, Nithipatikom K, Campbell WB

Authors

William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Sandra L. Pfister PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Angiotensin II
Animals
Aorta, Thoracic
Arachidonic Acid
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Imidazoles
Indomethacin
Isoprostanes
Male
Mesenteric Arteries
Models, Animal
Muscle, Smooth, Vascular
Rabbits
Receptors, Thromboxane
Superoxides
Vasoconstriction
Vasoconstrictor Agents