Ren L M, Nakane T, Chiba S
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
J Cardiovasc Pharmacol. 1993 Dec;22(6):841-6. doi: 10.1097/00005344-199312000-00010.
Using the cannula insertion method, we investigated the vascular responses of isolated simian coronary artery to acetylcholine (ACh). When the preparation was partially precontracted by 20 mM KCl, ACh and carbachol induced vasodilation dose dependently in coronary artery with endothelium, but ACh and carbachol contracted the coronary artery after removal of the endothelium by 1 mg saponin. A selective M1 receptor agonist 4-[N-(3-chlorophenyl)carbamoyloxy]-2-butinyltrimethylammonium++ + chloride (McN-A-343) did not affect the perfusion pressure of the precontracted coronary arteries significantly. Both these responses to ACh were inhibited by the M3 receptor antagonist 4-dipheny-lacetoxy N-methylpiperidine methobromide (4-DAMP) in a dose-dependent manner, but not by a selective M2 receptor antagonist AF-DX 116 (11-[[2-[(diethylamino)methyl]-1-piperidinyl] acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzo-diazepine-6-one). A selective M1 receptor antagonist pirenzepine did not affect ACh-induced vasoconstriction significantly and inhibited the vasodilation partially only at the highest dose (100 nmol). The effects of three antagonists on the vasodilative responses to carbachol were also studied and almost the same results were observed. Removal of the endothelium did not affect sodium nitroprusside (SNP)-induced vasodilation significantly. Pirenzepine, AF-DX 116, and 4-DAMP did not affect the action of isoproterenol. These data suggest that the vasodilation elicited by ACh is mediated by release of endothelium-derived relaxing factors (EDRF) consequent to the activation of M3 receptors on endothelial cells, and the constriction is mediated by stimulation of M3 receptors on smooth muscle cells in isolated simian coronary arteries.
采用套管插入法，我们研究了分离的猴冠状动脉对乙酰胆碱（ACh）的血管反应。当标本用20 mM氯化钾部分预收缩时，ACh和卡巴胆碱在有内皮的冠状动脉中剂量依赖性地诱导血管舒张，但在用1 mg皂苷去除内皮后，ACh和卡巴胆碱使冠状动脉收缩。选择性M1受体激动剂4-[N-(3-氯苯基)氨甲酰氧基]-2-丁炔基三甲基氯化铵（McN-A-343）对预收缩冠状动脉的灌注压力无明显影响。ACh的这两种反应均被M3受体拮抗剂4-二苯基乙酰氧基N-甲基哌啶甲基溴化物（4-DAMP）以剂量依赖性方式抑制，但未被选择性M2受体拮抗剂AF-DX 116（11-[[2-[(二乙氨基)甲基]-1-哌啶基]乙酰]-5,11-二氢-6H-吡啶并[2,3-b][1,4]苯并二氮杂䓬-6-酮）抑制。选择性M1受体拮抗剂哌仑西平对ACh诱导的血管收缩无明显影响，仅在最高剂量（100 nmol）时部分抑制血管舒张。还研究了三种拮抗剂对卡巴胆碱血管舒张反应的影响，观察到几乎相同的结果。去除内皮对硝普钠（SNP）诱导的血管舒张无明显影响。哌仑西平、AF-DX 116和4-DAMP对异丙肾上腺素的作用无影响。这些数据表明，ACh引起的血管舒张是由内皮细胞上M3受体激活后释放内皮源性舒张因子（EDRF）介导的，而收缩是由分离的猴冠状动脉平滑肌细胞上M3受体的刺激介导的。
