Auch-Schwelk W, Katusic Z S, Vanhoutte P M
Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota 55905.
Hypertension. 1989 Jun;13(6 Pt 2):859-64. doi: 10.1161/01.hyp.13.6.859.
To determine if oxygen-derived free radicals are mediators of endothelium-dependent contractions to acetylcholine in the aorta of spontaneously hypertensive rats (SHR), the mechanism of contraction to xanthine plus xanthine oxidase was studied. Rings, with and without endothelium, of thoracic aorta from normotensive Wistar-Kyoto (WKY) rats and SHR were suspended in organ chambers for isometric tension recording. Oxygen-derived free radicals caused concentration-dependent contractions; these contractions were twice as large in the aortas of SHR than in WKY rats. Deferoxamine reversed the response to xanthine oxidase to a small relaxation. Either allopurinol, superoxide dismutase, or catalase, or the combination of superoxide dismutase plus catalase reduced the contractions. Diltiazem inhibited the response to xanthine oxidase; in contrast, phentolamine plus propranolol did not affect it. Indomethacin and meclofenamate, but not tranylcypromine or dazoxiben blocked the contractions. Endothelium-dependent contractions to acetylcholine in aortas from the SHR were not affected by deferoxamine or superoxide dismutase plus catalase. These data suggest that hydroxyl radicals cause contractions in the rat aorta, which are dependent on extracellular calcium and mediated by activation of the cyclooxygenase in the vascular smooth muscle. The augmented contractions in the hypertensive strain are due to an increased reactivity of the smooth muscle to oxygen-derived free radicals. However, the lack of effect of the scavengers on endothelium-dependent contractions to acetylcholine suggests that the endothelium-derived contracting factor is chemically different from oxygen-derived free radicals.
为了确定氧衍生的自由基是否是自发性高血压大鼠（SHR）主动脉中内皮依赖性乙酰胆碱收缩的介质，研究了黄嘌呤加黄嘌呤氧化酶的收缩机制。将来自正常血压的Wistar-Kyoto（WKY）大鼠和SHR的胸主动脉有内皮和无内皮的血管环悬挂在器官浴槽中进行等长张力记录。氧衍生的自由基引起浓度依赖性收缩；这些收缩在SHR主动脉中比在WKY大鼠中大一倍。去铁胺将对黄嘌呤氧化酶的反应逆转至轻微舒张。别嘌呤醇、超氧化物歧化酶或过氧化氢酶，或超氧化物歧化酶加过氧化氢酶的组合可减少收缩。地尔硫卓抑制对黄嘌呤氧化酶的反应；相反，酚妥拉明加普萘洛尔对其无影响。吲哚美辛和甲氯芬那酸可阻断收缩，但反苯环丙胺或达唑氧苯则不能。SHR主动脉中对乙酰胆碱的内皮依赖性收缩不受去铁胺或超氧化物歧化酶加过氧化氢酶的影响。这些数据表明，羟基自由基在大鼠主动脉中引起收缩，这依赖于细胞外钙并由血管平滑肌中环氧化酶的激活介导。高血压品系中增强的收缩是由于平滑肌对氧衍生自由基的反应性增加。然而，清除剂对乙酰胆碱内皮依赖性收缩缺乏影响表明，内皮衍生的收缩因子在化学性质上与氧衍生的自由基不同。
