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.

[1]  E. Ellis,et al.  Isoprostanes: free radical-generated prostaglandins with constrictor effects on cerebral arterioles. , 1997, Stroke.

[2]  J. McMurray,et al.  Effects of a Xanthine Oxidase/Hypoxanthine Free Radical and Reactive Oxygen Species Generating System on Endothelial Function in New Zealand White Rabbit Aortic Rings , 1993, Journal of cardiovascular pharmacology.

[3]  J. Weiss,et al.  Oxygen free radicals and cardiac reperfusion abnormalities. , 1992, Hypertension.

[4]  R. Sharma,et al.  Immunolocalization of native antioxidant scavenger enzymes in early hypertensive and atherosclerotic arteries. Role of oxygen free radicals. , 1992, Arteriosclerosis and thrombosis : a journal of vascular biology.

[5]  E. Lakatta,et al.  Study of the mechanisms of hydrogen peroxide and hydroxyl free radical-induced cellular injury and calcium overload in cardiac myocytes. , 1991, The Journal of biological chemistry.

[6]  S. Moncada,et al.  Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo , 1990, British journal of pharmacology.

[7]  R. Bolli.  Mechanism of Myocardial “Stunning” , 1990, Circulation.

[8]  L. Buja,et al.  Free radicals alter ionic calcium levels and membrane phospholipids in cultured rat ventricular myocytes. , 1990, Journal of molecular and cellular cardiology.

[9]  Z. Katušić,et al.  Thromboxane A2 Receptor Antagonists Inhibit Endothelium‐Dependent Contractions , 1990, Hypertension.

[10]  B. Lucchesi,et al.  Myocardial ischemia, reperfusion and free radical injury. , 1990, The American journal of cardiology.

[11]  J. Mehta,et al.  Superoxide radical-mediated endothelial injury and vasoconstriction of rat thoracic aortic rings. , 1990, The Journal of laboratory and clinical medicine.

[12]  K. Okumura,et al.  Prostaglandin H2 may be the endothelium-derived contracting factor released by acetylcholine in the aorta of the rat. , 1990, Hypertension.

[13]  S. Wilson,et al.  Role of oxygen-derived free radicals in acute angiotensin II--induced hypertensive vascular disease in the rat. , 1990, Circulation research.

[14]  R. Kloner,et al.  Deleterious Effects of Oxygen Radicals in Ischemia/Reperfusion Resolved and Unresolved Issues , 1989, Circulation.

[15]  Z. Katušić,et al.  Contractions to Oxygen‐Derived Free Radicals Are Augmented in Aorta of the Spontaneously Hypertensive Rat , 1989, Hypertension.

[16]  J. Weiss,et al.  Effects of exogenous free radicals on electromechanical function and metabolism in isolated rabbit and guinea pig ventricle. Implications for ischemia and reperfusion injury. , 1989, The Journal of clinical investigation.

[17]  R. Kloner,et al.  “Reperfusion Injury” by Oxygen‐Derived Free Radicals?: Effect of Superoxide Dismutase Plus Catalase, Given at the Time of Reperfusion, on Myocardial Infarct Size, Contractile Function, Coronary Microvasculature, and Regional Myocardial Blood Flow , 1989, Circulation research.

[18]  K. Okumura,et al.  Myocardial salvage by a novel thromboxane A2 synthetase inhibitor in a canine coronary occlusion-reperfusion model. , 1988, Arzneimittel-Forschung.

[19]  P. Ramwell,et al.  Induction of vascular relaxation by hydroperoxides. , 1986, Biochemical and biophysical research communications.

[20]  S. Moncada,et al.  Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor , 1986, Nature.

[21]  D. Dewitt,et al.  Superoxide generation and reversal of acetylcholine-induced cerebral arteriolar dilation after acute hypertension. , 1985, Circulation research.

[22]  J. Repine,et al.  Oxygen metabolites stimulate thromboxane production and vasoconstriction in isolated saline-perfused rabbit lungs. , 1984, The Journal of clinical investigation.

[23]  B. Halliwell,et al.  Oxygen toxicity, oxygen radicals, transition metals and disease. , 1984, The Biochemical journal.

[24]  M. Kawamura,et al.  Highly selective inhibitors of thromboxane synthetase. 1. Imidazole derivatives. , 1981, Journal of medicinal chemistry.

[25]  W. Powell.  Rapid extraction of oxygenated metabolites of arachidonic acid from biological samples using octadecylsilyl silica. , 1980, Prostaglandins.

[26]  A. Johnson.  Human pulmonary endothelial cells in culture. Activities of cells from arteries and cells from veins. , 1980, The Journal of clinical investigation.

[27]  B. Jaffe,et al.  Radioimmunoassay measurement of prostaglandins E, A, and F in human plasma. , 1973, The Journal of clinical investigation.

[28]  G. Rubanyi,et al.  Vascular effects of oxygen-derived free radicals. , 1988, Free radical biology & medicine.