Oxygen-derived free radical-induced vasoconstriction by thromboxane A2 in aorta of the spontaneously hypertensive rat.
This study was performed to clarify the mechanism of vasoconstriction induced by oxygen-derived free radicals in spontaneously hypertensive rats. The isometric tension of aortic rings from spontaneously hypertensive rats and Wistar-Kyoto rats was measured in Krebs-Henseleit solution. Oxygen-derived free radicals were generated by mixing xanthine and xanthine oxidase. The removal of endothelium enhanced the contractions induced by oxygen-derived free radicals. The inhibition of nitric oxide production with NG-nitro-L-arginine methyl ester (10(-4) M) enhanced the contractions. Treatment with the thromboxane A2 (TXA2) synthetase inhibitor OKY-046 (10(-4) M) or RS-5186 (10(-4) M) markedly reduced the contractions. Treatment with the cyclooxygenase inhibitor indomethacin (10(-5) M) and a TXA2/prostaglandin H2 (PGH2) receptor antagonist, ONO-3708 (10(-6) M), completely abolished the oxygen-derived free radical-induced contractions. In contrast, treatment with the PGI2 synthetase inhibitor tranylcypromine (10(-4) M) did not attenuate the oxygen-derived free radical-induced contractions. Whether endothelium was present or not, the release of TXB2, PGE2, and 6-keto-PGF1alpha, but not PGF2alpha, was increased by the production of oxygen-derived free radicals. Catalase and the hydroxyl radical scavenger deferoxamine plus mannitol markedly inhibited the oxygen-derived free radical-induced contractions. These results suggest that oxygen-derived free radical-induced vasoconstriction in spontaneously hypertensive rat aorta is caused by TXA2 and PGH2 released in smooth muscle.
Hibino
M
M
Internal Medicine II, Nagoya University School of Medicine, Japan.
Okumura
K
K
Iwama
Y
Y
Mokuno
S
S
Osanai
H
H
Matsui
H
H
Toki
Y
Y
Ito
T
T
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000503:physiopathology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000494:pharmacology*; D006973:Hypertension / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D010100:Oxygen / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013928:Thromboxane A2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014661:Vasoconstriction / Q000187:drug effects*
D016861:Cyclooxygenase Inhibitors; D016166:Free Radical Scavengers; D005609:Free Radicals; D011453:Prostaglandins; D009569:Nitric Oxide; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase; D010100:Oxygen