la Rochelle C D, Richard V, Dubois-Randé J L, Roupie E, Giudicelli J F, Hittinger L, Berdeaux A
Département de Pharmacologie, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, France.
J Pharmacol Exp Ther. 1992 Dec;263(3):1091-6.
Cromakalim and pinacidil, two potassium channel openers, dilate both large and small coronary arteries in conscious dogs. Because flow-mediated dilation of large arteries is endothelium-dependent, the consequences of in vivo endothelium removal (balloon denudation) on the response of large epicardial coronary arteries to cromakalim (10 micrograms/kg) and pinacidil (30 micrograms/kg) were investigated in six dogs chronically instrumented for the measurement of arterial pressure, left circumflex coronary artery diameter and coronary blood flow. Endothelium removal abolished the dilation of large coronary arteries induced by acetylcholine (endothelium-dependent dilation) and reactive hyperemia (flow-mediated dilation), but only slightly reduced (-18%) that induced by nitroglycerin. Before endothelium removal, both cromakalim and pinacidil induced a significant decrease in coronary resistance (-71 +/- 2 and -63 +/- 2%, respectively) and a significant increase in coronary diameter (8.5 +/- 1.3 and 6.7 +/- 0.9%). After endothelium removal, the decreases in coronary resistance were unaffected, but the increases in coronary diameter were reduced by 93 and 98% as compared to predenudation responses with cromakalim and pinacidil, respectively (both P < .01). In contrast, in vitro studies performed in isolated large epicardial coronary arteries obtained from five additional dogs showed that cromakalim evoked relaxations that were not affected by prior in vivo endothelium removal. Thus, despite the presence of potassium channels in isolated denuded large coronary arteries, our data demonstrate that cromakalim- and pinacidil-induced dilation of large arteries in vivo is an indirect, flow-mediated effect which is entirely endothelium-dependent.
两种钾通道开放剂——克罗卡林和吡那地尔，可使清醒犬的大、小冠状动脉扩张。由于大动脉的血流介导性扩张依赖于内皮，因此在六只长期植入用于测量动脉血压、左旋冠状动脉直径和冠状动脉血流量的犬中，研究了体内去除内皮（球囊剥脱）对大的心外膜冠状动脉对克罗卡林（10微克/千克）和吡那地尔（30微克/千克）反应的影响。去除内皮消除了乙酰胆碱诱导的大冠状动脉扩张（内皮依赖性扩张）和反应性充血（血流介导性扩张），但仅轻微降低了硝酸甘油诱导的扩张（降低18%）。在去除内皮之前，克罗卡林和吡那地尔均导致冠状动脉阻力显著降低（分别为-71±2%和-63±2%），冠状动脉直径显著增加（8.5±1.3%和6.7±0.9%）。去除内皮后，冠状动脉阻力的降低不受影响，但与克罗卡林和吡那地尔剥脱前反应相比，冠状动脉直径的增加分别减少了93%和98%（均P<0.01）。相反，在另外五只犬的离体大的心外膜冠状动脉上进行的体外研究表明，克罗卡林引起的舒张不受先前体内去除内皮的影响。因此，尽管在离体剥脱的大冠状动脉中存在钾通道，但我们的数据表明，克罗卡林和吡那地尔在体内诱导的大动脉扩张是一种间接的、血流介导的效应，且完全依赖于内皮。
