TY - JOUR T1 - Oxidative Stress Induced by <em>tert</em>-Butyl Hydroperoxide Causes Vasoconstriction in the Aorta from Hypertensive and Aged Rats: Role of Cyclooxygenase-2 Isoform JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 75 LP - 81 VL - 293 IS - 1 AU - Edith-Clara Garcia-Cohen AU - Jesus Marin AU - Luis D. Diez-Picazo AU - Ana B. Baena AU - Mercedes Salaices AU - M. Angeles Rodriguez-Martinez Y1 - 2000/04/01 UR - http://jpet.aspetjournals.org/content/293/1/75.abstract N2 - We analyzed the mechanisms involved in the effect oftert-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 inhibitorsNG-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 H2/thromboxane A2receptor 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 thet-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-A2, probably prostaglandin-H2, 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 thet-BOOH-induced vasoconstriction in WKY, with this modulator role lost in SHR. The American Society for Pharmacology and Experimental Therapeutics ER -