Clozel J P, Sprecher U
Pharmaceutical Research Department, F. Hoffmann-La Roche, Basel, Switzerland.
Am J Physiol. 1991 Mar;260(3 Pt 2):H893-901. doi: 10.1152/ajpheart.1991.260.3.H893.
The goal of this study was to evaluate the influence of low coronary perfusion pressure on the coronary vasoconstriction induced by endothelin. For this purpose, the circumflex coronary arteries of 12 open-chest dogs were cannulated and perfused at a controlled pressure. Total coronary blood flow was measured with an electromagnetic flowmeter and the transmural distribution of coronary blood flow with the radioactive microspheres technique. In addition, the circumflex coronary artery diameter was measured by sonomicrometry with piezoelectric crystals, and the coronary cross-sectional area was calculated. At a coronary perfusion pressure of 100 mmHg, endothelin induced a marked coronary vasoconstriction and a redistribution of coronary blood flow toward the endocardium. At a low coronary perfusion pressure of 40 mmHg, these effects of endothelin were still present. The constriction of the large coronary artery occurred even with a lower dose of endothelin at a low coronary perfusion pressure compared with the normal perfusion pressure. This was not the case when angiotensin II was given the same way. We conclude that endothelin is a potent coronary vasoconstrictor even at a low perfusion pressure. Thus one may speculate that endothelin plays a role in the coronary spasm which has been shown in patients with angina pectoris.
本研究的目的是评估低冠状动脉灌注压对内皮素诱导的冠状动脉血管收缩的影响。为此，对12只开胸犬的左旋冠状动脉进行插管，并在控制压力下进行灌注。用电磁流量计测量冠状动脉总血流量，用放射性微球技术测量冠状动脉血流量的跨壁分布。此外，用压电晶体通过超声测量仪测量左旋冠状动脉直径，并计算冠状动脉横截面积。在冠状动脉灌注压为100 mmHg时，内皮素可引起明显的冠状动脉血管收缩，并使冠状动脉血流重新分布至心内膜。在冠状动脉灌注压低至40 mmHg时，内皮素的这些作用仍然存在。与正常灌注压相比，在低冠状动脉灌注压下，即使使用较低剂量的内皮素也会发生大冠状动脉的收缩。以同样方式给予血管紧张素II时则并非如此。我们得出结论，即使在低灌注压下，内皮素仍是一种有效的冠状动脉血管收缩剂。因此可以推测，内皮素在心绞痛患者中出现的冠状动脉痉挛中起作用。
