Forman R, Kirk E S
Cardiovasc Res. 1980 Oct;14(10):601-6. doi: 10.1093/cvr/14.10.601.
One of the mechanisms whereby nitroglycerin is considered to reduce myocardial ischaemia and spasm is its preferential reduction of resistance of large compared with small coronary arteries. Accordingly, the action of nitroglycerin on these two resistance beds was compared with newer coronary vasodilator drugs. Following intracoronary administration of boluses of each drug, large and small vessel coronary resistance was measured in 14 dogs by recording the pressure drop across each vascular bed while flow was held constant. The dose of each drug was given to reduce small vessel resistance by 30% (range means 27 to 32%) which peaked at 5 to 10 s and declined to 8 to 18% at 1 min when reduction in large vessel resistance was at its maximum. At 1 min the large vessel resistance was decreased 56 +/- 5% by nitroglycerin, 23 +/- 5% by nitroprusside, 8 +/- 4% by perhexiline, 0 +/- 5% by verapamil and increased 8 +/- 5% by nifedipine. Nitroprusside reduced the large vessel resistance significantly less than nitroglycerin (P < 0.001) for an equivalent reduction in small vessel resistance. Perhexiline, verapamil and nifedipine did not significantly reduce large vessel resistance and the discrepancy between these results and their antianginal and antispasm effect in humans was not apparent from these experiments. However, a suitable model of coronary spasm in the dog following ergonovine injection could not be created.
硝酸甘油被认为可减轻心肌缺血和痉挛的机制之一是，与小冠状动脉相比，它能优先降低大冠状动脉的阻力。因此，将硝酸甘油对这两个阻力血管床的作用与新型冠状动脉扩张剂进行了比较。在向每只狗冠状动脉内注射每种药物的大剂量后，通过在血流保持恒定的情况下记录每个血管床的压力降，测量了14只狗的大、小血管冠状动脉阻力。给予每种药物的剂量以降低小血管阻力30%（范围为27%至32%），在5至10秒时达到峰值，在1分钟时降至8%至18%，此时大血管阻力降低到最大。在1分钟时，硝酸甘油使大血管阻力降低56±5%，硝普钠降低23±5%，哌克昔林降低8±4%，维拉帕米降低0±5%，硝苯地平使大血管阻力增加8±5%。对于同等程度的小血管阻力降低，硝普钠使大血管阻力降低的幅度明显小于硝酸甘油（P<0.001）。哌克昔林、维拉帕米和硝苯地平并未显著降低大血管阻力，从这些实验中也看不出这些结果与它们在人体中的抗心绞痛和抗痉挛作用之间的差异。然而，注射麦角新碱后在狗身上未能建立合适的冠状动脉痉挛模型。
