Sellke F W, Tomanek R J, Harrison D G
Department of Surgery, University of Iowa College of Medicine, Iowa City.
J Pharmacol Exp Ther. 1991 Jul 1;258(1):365-9.
Nitroglycerin potently dilates large coronary arteries but has minimal effect on coronary resistance vessels. Thus, nitroglycerin is not likely to be converted to vasoactive intermediates in small coronary microvessels (less than 100 microns diameter). Because nitroglycerin biotransformation may involve sulfhydryl groups, the effect of L-cysteine on the dilation caused by nitroglycerin (1 nM to 10 microM) was examined in small (80-100 microns in diameter) and large (190-300 microns in diameter) porcine coronary microvessels. Vessels were pressurized in a no-flow state and preconstricted with acetylcholine, then visualized by means of an in vitro microvessel imaging apparatus. Under control conditions, nitroglycerin caused potent dilations of large coronary microvessels, while having minimal effects on small coronary microvessels [peak relaxations 90 +/- 3 vs. 20 +/- 7% (mean +/- S.E.M.) of preconstricted diameter, respectively]. L-Cysteine (100 microM) markedly enhanced relaxations of small coronary microvessels (peak relaxation 96 +/- 2%), while having no effect on relaxations of large coronary microvessels. Ethacrynic acid, which alkylates sulfhydryl groups, markedly inhibited relaxations of large coronary microvessels (peak relaxation = 31 +/- 9%) yet had a minimal effect on the small relaxations of small coronary microvessels to nitroglycerin. Thus, when sulfhydryl groups are made available, small coronary microvessels are markedly responsive to nitroglycerin. This suggests that small coronary microvessels normally lack the reductive capacity to convert nitroglycerin to its active metabolites. Prussian blue stains of sulfhydryl groups in large and small coronary microvessels were qualitatively similar. Thus, small coronary microvessels do not lack sulfhydryl groups but may be deficient in a critical pool necessary for nitroglycerin biotransformation.
硝酸甘油能有效扩张大冠状动脉，但对冠状动脉阻力血管影响极小。因此，硝酸甘油不太可能在小冠状动脉微血管（直径小于100微米）中转化为血管活性中间体。由于硝酸甘油的生物转化可能涉及巯基，因此在猪的小（直径80 - 100微米）和大（直径190 - 300微米）冠状动脉微血管中研究了L - 半胱氨酸对硝酸甘油（1 nM至10 microM）引起的舒张作用的影响。血管在无血流状态下加压并用乙酰胆碱预收缩，然后通过体外微血管成像设备进行观察。在对照条件下，硝酸甘油能有效扩张大冠状动脉微血管，而对小冠状动脉微血管影响极小[预收缩直径的峰值舒张分别为90±3%和20±7%（平均值±标准误）]。L - 半胱氨酸（100 microM）显著增强了小冠状动脉微血管的舒张（峰值舒张为96±2%），而对大冠状动脉微血管的舒张没有影响。能使巯基烷基化的依他尼酸显著抑制了大冠状动脉微血管的舒张（峰值舒张 = 31±9%），但对小冠状动脉微血管对硝酸甘油的微小舒张影响极小。因此，当有巯基时，小冠状动脉微血管对硝酸甘油有明显反应。这表明小冠状动脉微血管通常缺乏将硝酸甘油转化为其活性代谢物的还原能力。大、小冠状动脉微血管中巯基的普鲁士蓝染色在质量上相似。因此，小冠状动脉微血管并不缺乏巯基，但可能缺乏硝酸甘油生物转化所需的关键储备。
