Oxidative Stress Induced by tert-Butyl Hydroperoxide Causes Vasoconstriction in the Aorta from Hypertensive and Aged Rats: Role of Cyclooxygenase-2 Isoform

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 293; no. 1; p. 75
• Main Authors: Edith-Clara Garcia-Cohen, Jesus Marin, Luis D. Diez-Picazo, Ana B. Baena, Mercedes Salaices, M. Angeles Rodriguez-Martinez
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.04.2000
• Subjects: Aging - physiology; Animals; Aorta, Thoracic - drug effects; Aorta, Thoracic - enzymology; Blotting, Western; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; Endothelium, Vascular; Enzyme Inhibitors - pharmacology; Hypertension - genetics; Hypertension - physiopathology; Indomethacin - pharmacology; Isoenzymes - physiology; Male; Muscle, Smooth, Vascular - drug effects; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase Type III; Oxidative Stress - drug effects; Oxidative Stress - physiology; Prostaglandin-Endoperoxide Synthases - physiology; Rats; Rats, Inbred SHR; Rats, Inbred WKY; tert-Butylhydroperoxide - toxicity; Time Factors; Vasoconstriction - drug effects
• ISSN: 0022-3565; 1521-0103

We analyzed the mechanisms involved in the effect of tert -butyl hydroperoxide ( t -BOOH) in isolated aortic rings with and without endothelium from normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) at 6, 18, and 24 months of age. t -BOOH (1 μM-10 mM) induced concentration-dependent contractions that were scarcely modified by aging and potentiated in SHR and by endothelium removal. The nitric oxide synthase and prostacyclin synthase inhibitors N G -nitro- l -arginine methyl ester (100 μM) and tranylcypromine (100 μM), respectively, increased both basal tone and the t -BOOH-induced contractions in intact segments from WKY, with these effects not observed in SHR. Indomethacin (10 μM), a nonspecific cyclooxygenase inhibitor, and SQ 29,548 (10 μM), a prostaglandin H 2 /thromboxane A 2 receptor blocker, abolished the t -BOOH-induced vasoconstriction, independent of age and hypertension. In both strains, these contractile responses were unaltered by the thromboxane synthase inhibitor imidazole (10 μM). The cyclooxygenase-2 inhibitor NS-398 (10 μM) abolished or markedly reduced the t -BOOH-induced contractions in segments with or without endothelium, respectively. In addition, expression of cyclooxygenase-2 protein was detected in aorta from WKY and SHR in either basal condition or after stimulation with t -BOOH. These results suggest that (1) t -BOOH-induced vasoconstriction in the aorta from WKY and SHR is essentially mediated by cyclooxygenase-2 metabolites, different from thromboxane-A 2 , probably prostaglandin-H 2 , and/or isoprostanes; (2) aging scarcely modifies, whereas endothelium negatively modulates, these contractions in both strains; and (3) nitric oxide and prostacyclin exert a negative modulator role on the t -BOOH-induced vasoconstriction in WKY, with this modulator role lost in SHR.