Wheatley R M, Dockery S P, Kurz M A, Sayegh H S, Harrison D G
Department of Medicine, Emory University, Atlanta, Georgia 30322.
Am J Physiol. 1994 Jan;266(1 Pt 2):H291-7. doi: 10.1152/ajpheart.1994.266.1.H291.
Previous studies have shown the effect of nitroglycerin on coronary microvessels < 100 microns in diameter is markedly enhanced by L-cysteine. These studies were performed to examine the mechanisms responsible for this effect. Under control conditions, nitroglycerin caused potent dilations of large (> 200 microns diam) coronary microvessels while having minimal effects on small (< 100 microns diam) coronary microvessels [peak relaxations 85 +/- 4 vs. 23 +/- 3% (mean +/- SE) of endothelin-1-constricted vessels, respectively]. L-Cysteine (100 microM) and N-acetylcysteine (100 microM) markedly enhanced nitroglycerin-induced relaxations of small coronary microvessels (peak relaxation 84 +/- 6 and 87 +/- 12%, respectively) while having no effect on relaxations of vessels > 100 microns. In contrast, neither L-methionine (100 microM) nor glutathione (100 microM) enhanced nitroglycerin's vasodilation of small coronary microvessels. The effects of L-cysteine and N-acetylcysteine on the augmentation of nitroglycerin vasodilatation in smaller coronary microvessels was abolished in the presence of buthionine sulfoximine (100 microM), a potent inhibitor of intracellular glutathione synthesis. Buthionine sulfoximine had no effect on the vasodilatation produced by nitroprusside. These data demonstrate that, in smaller coronary microvessels, L-cysteine and N-acetylcysteine enhance nitroglycerin-induced vasodilatation by increasing intracellular glutathione concentrations. Intracellular glutathione, formed from either L-cysteine or N-acetylcysteine, may participate in the formation of an intermediate of nitroglycerin biotransformation or may maintain a redox potential within coronary microvessels that favors enzymatic bioconversion of nitroglycerin.
先前的研究表明，L-半胱氨酸可显著增强硝酸甘油对直径小于100微米的冠状动脉微血管的作用。进行这些研究是为了探究造成这种作用的机制。在对照条件下，硝酸甘油可使直径较大（>200微米）的冠状动脉微血管产生强烈舒张，而对直径较小（<100微米）的冠状动脉微血管作用极小[分别为内皮素-1收缩血管的峰值舒张率85±4%与23±3%（平均值±标准误）]。L-半胱氨酸（100微摩尔）和N-乙酰半胱氨酸（100微摩尔）可显著增强硝酸甘油诱导的小冠状动脉微血管舒张（峰值舒张率分别为84±6%和87±12%），而对直径大于100微米的血管舒张无影响。相比之下，L-蛋氨酸（100微摩尔）和谷胱甘肽（100微摩尔）均未增强硝酸甘油对小冠状动脉微血管的血管舒张作用。在存在丁硫氨酸亚砜胺（100微摩尔）（一种细胞内谷胱甘肽合成的强效抑制剂）的情况下，L-半胱氨酸和N-乙酰半胱氨酸对较小冠状动脉微血管中硝酸甘油血管舒张增强作用消失。丁硫氨酸亚砜胺对硝普钠产生的血管舒张无影响。这些数据表明，在较小冠状动脉微血管中，L-半胱氨酸和N-乙酰半胱氨酸通过增加细胞内谷胱甘肽浓度来增强硝酸甘油诱导的血管舒张。由L-半胱氨酸或N-乙酰半胱氨酸形成的细胞内谷胱甘肽可能参与硝酸甘油生物转化中间体的形成，或可能维持冠状动脉微血管内有利于硝酸甘油酶促生物转化的氧化还原电位。
