Kurz M A, Lamping K G, Bates J N, Eastham C L, Marcus M L, Harrison D G
Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City.
Circ Res. 1991 Mar;68(3):847-55. doi: 10.1161/01.res.68.3.847.
Nitroglycerin dilates large (greater than or equal to 100 microns) but not small coronary arterial microvessels, and a putative metabolite of nitroglycerin, S-nitroso-L-cysteine, has been shown in vitro to dilate both large and small coronary microvessels. Based on this evidence, we tested the hypothesis that the lack of response of small coronary microvessels was due to an inability of small coronary microvessels to convert nitroglycerin into its vasoactive metabolite and examined possible explanations for this phenomenon. We studied left ventricular epicardial microvessels in vivo using video microscopy and stroboscopic epi-illumination in anesthetized, open-chest dogs. Diameters were determined while the epicardium was suffused with nitroglycerin, S-nitroso-L-cysteine, or S-nitroso-D-cysteine (all 10 microM) and nitroglycerin in the presence of L- or D-cysteine (100 microM). None of the agents affected systemic hemodynamics. Nitroglycerin dilated large arterioles (20 +/- 2%) but not small arterioles (1 +/- 1%). Both S-nitroso-L-cysteine and S-nitroso-D-cysteine were potent dilators of all size classes of microvessels. Concomitant application of L-cysteine and nitroglycerin evoked dilation in small microvessels (22 +/- 4%, p less than 0.5 versus nitroglycerin alone) and larger microvessels (27 +/- 6%, p = NS versus nitroglycerin alone). D-Cysteine did not alter the microvascular response to nitroglycerin in either small (7 +/- 4%, p = NS versus nitroglycerin alone) or large (18 +/- 3%, p = NS versus nitroglycerin alone) microvessels. Neither L-cysteine nor D-cysteine had a direct effect on microvascular diameter. These findings suggest that 1) sulfhydryl groups are required for the conversion of nitroglycerin to its vasoactive metabolite; 2) the interaction between nitroglycerin and sulfhydryl residues is a stereospecific process, indicating either an intracellular mechanism or a membrane-associated enzymatic reaction; and 3) a lack of available sulfhydryl groups may be responsible for the lack of response of small coronary arterioles to nitroglycerin.
硝酸甘油可扩张大的（大于或等于100微米）而非小的冠状动脉微血管，并且硝酸甘油的一种假定代谢产物S-亚硝基-L-半胱氨酸在体外已被证明可扩张大、小冠状动脉微血管。基于此证据，我们检验了以下假设：小冠状动脉微血管缺乏反应是由于其无法将硝酸甘油转化为血管活性代谢产物，并研究了对此现象的可能解释。我们在麻醉的开胸犬体内使用视频显微镜和频闪落射照明研究左心室心外膜微血管。在向心外膜灌注硝酸甘油、S-亚硝基-L-半胱氨酸或S-亚硝基-D-半胱氨酸（均为10微摩尔）以及在L-或D-半胱氨酸（100微摩尔）存在下灌注硝酸甘油时测定血管直径。这些药物均未影响全身血流动力学。硝酸甘油可扩张大的小动脉（20±2%），但不扩张小的小动脉（1±1%）。S-亚硝基-L-半胱氨酸和S-亚硝基-D-半胱氨酸都是所有大小类别的微血管的强效扩张剂。同时应用L-半胱氨酸和硝酸甘油可引起小微血管（22±4%，与单独使用硝酸甘油相比p<0.5）和较大微血管（27±6%，与单独使用硝酸甘油相比p=无显著性差异）扩张。D-半胱氨酸在小微血管（7±4%，与单独使用硝酸甘油相比p=无显著性差异）或大微血管（18±3%，与单独使用硝酸甘油相比p=无显著性差异）中均未改变微血管对硝酸甘油的反应。L-半胱氨酸和D-半胱氨酸对微血管直径均无直接影响。这些发现表明：1）硝酸甘油转化为血管活性代谢产物需要巯基；2）硝酸甘油与巯基残基之间的相互作用是一个立体特异性过程，表明存在细胞内机制或与膜相关的酶促反应；3）缺乏可用的巯基可能是小冠状动脉小动脉对硝酸甘油缺乏反应的原因。
