Bauer B, Neubauer S, Spindler M, Dürr R, Becker H H, Ertl G
Medizinische Klinik, University of Würzburg, Germany.
J Cardiovasc Pharmacol. 1995 May;25(5):756-62. doi: 10.1097/00005344-199505000-00011.
The coronary effects of angiotensin-converting enzyme (ACE) inhibitors and their mechanisms of action are not well understood. Because these drugs may interfere with hormone systems other than the reninangiotensin system (RAS), we studied modulation of the coronary effects of neurotensin, neuropeptide Y (NPY), and endothelin-1 (ET-1) by pretreatment with captopril in anesthetized, open-chest dogs. The left anterior descending coronary artery (LAD) was cannulated and perfused at a pressure equal to mean aortic blood pressure. Coronary blood flow (CBF) was measured by an electromagnetic flowmeter, subendocardial segment length by ultrasonic crystals. ACE inhibition (captopril 0.25 mg/kg), as an intracoronary (i.c.) injection, followed by an intracoronary infusion (0.25 mg/kg/h) did not affect the relative vasoconstrictor effects of ET-1 (10(-4)-10(-1) micrograms/kg i.c.) or neuropeptide Y (10(-3)-1 microgram/kg i.c.). However preinjection flow of a second dose-response curve of ET-1 was significantly higher in captopril-treated as compared with control animals. The increase in CBF induced by neurotensin (10(-3)-1 microgram/kg i.c.) was potentiated by captopril (40 +/- 14% after vs. 20 +/- 9% before captopril, p < 0.01, at the highest dose used). Changes in hemodynamics or in regional myocardial function could not explain altered effects of neurotensin. We therefore conclude that ACE inhibition does not interfere with the acute vasoconstrictor effects of ET-1 or NPY in this canine model but may reverse the long-term tonic coronary constrictor effect of ET-1. Potentiation of the neurotensin effect on CBF might be due to prevention of hydrolysis of neurotensin or to a cyclooxygenase-dependent mechanism.
血管紧张素转换酶（ACE）抑制剂的冠状动脉效应及其作用机制尚未完全明确。由于这些药物可能会干扰肾素 - 血管紧张素系统（RAS）以外的激素系统，我们在麻醉的开胸犬中研究了卡托普利预处理对神经降压素、神经肽Y（NPY）和内皮素 - 1（ET - 1）冠状动脉效应的调节作用。将左冠状动脉前降支（LAD）插管，并在等于平均主动脉血压的压力下进行灌注。通过电磁流量计测量冠状动脉血流量（CBF），通过超声晶体测量心内膜下节段长度。冠状动脉内注射（i.c.）ACE抑制剂（卡托普利0.25mg/kg），随后冠状动脉内输注（0.25mg/kg/h），并不影响ET - 1（10^(-4)-10^(-1)微克/千克i.c.）或神经肽Y（10^(-3)-1微克/千克i.c.）的相对血管收缩效应。然而，与对照动物相比，卡托普利治疗组中ET - 1第二剂量 - 反应曲线的注射前血流量显著更高。神经降压素（10^(-3)-1微克/千克i.c.）诱导的CBF增加在卡托普利作用下得到增强（在最高使用剂量下，卡托普利给药后为40±14%，给药前为20±9%，p<0.01）。血流动力学或局部心肌功能的变化无法解释神经降压素效应的改变。因此，我们得出结论，在该犬模型中，ACE抑制并不干扰ET - 1或NPY的急性血管收缩效应，但可能会逆转ET - 1的长期冠状动脉紧张性收缩效应。神经降压素对CBF效应的增强可能是由于防止了神经降压素的水解或依赖于环氧化酶的机制。
