Kawahara K, Satoh H, Inui J
Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Saitama, Japan.
Nihon Yakurigaku Zasshi. 1988 Dec;92(6):397-410. doi: 10.1254/fpj.92.397.
Cardiovascular effects of nitrendipine were examined in anesthetized dogs, blood-perfused canine papillary muscles and isolated arteries. In anesthetized dogs, nitrendipine by intravenous (0.3-10 micrograms/kg) or intraduodenal (0.1 mg/kg) administration lowered blood pressure and increased coronary and vertebral blood flow. Nitrendipine also decreased the difference in oxygen concentrations between arterial and coronary sinus blood, which indicates that nitrendipine increased the oxygen supply to the heart. Myocardial oxygen consumption was slightly increased at a low dose (3 micrograms/kg, i.v.) accompanied with a small increase in max dP/dt, but was decreased at high doses (30-100 micrograms/kg, i.v.). A negative inotropic effect was observed in blood-perfused canine papillary muscles. However, nitrendipine is thought to be highly vasoselective because much higher doses were required to decrease the myocardial contraction than to increase the coronary blood flow. Furthermore, nitrendipine suppressed the contraction induced by KCl, acetylcholine, histamine, norepinephrine, 5-hydroxytryptamine and prostaglandin F2 alpha of porcine coronary arteries, and the rhythmic contraction induced by 3,4-diaminopyridine of canine coronary arteries. In isolated rabbit aortic preparations, nitrendipine strongly inhibited the KCl-induced contraction, but not the phenylephrine-induced contraction. These effects of nitrendipine were almost similar to those of nifedipine. It is suggested that nitrendipine decreases afterload (blood pressure), increases the blood flow and oxygen supply to the heart, and inhibits coronary spasm, which is due to the calcium antagonistic effect. Nitrendipine may be useful for the treatment of ischemic heart diseases.
在麻醉犬、血液灌流的犬乳头肌和离体动脉中研究了尼群地平的心血管效应。在麻醉犬中,静脉注射(0.3 - 10微克/千克)或十二指肠内给予(0.1毫克/千克)尼群地平可降低血压,并增加冠状动脉和椎动脉血流量。尼群地平还可降低动脉血与冠状窦血之间的氧浓度差值,这表明尼群地平增加了心脏的氧供应。低剂量(静脉注射3微克/千克)时心肌耗氧量略有增加,同时最大dP/dt略有增加,但高剂量(静脉注射30 - 100微克/千克)时心肌耗氧量降低。在血液灌流的犬乳头肌中观察到负性肌力作用。然而,尼群地平被认为具有高度血管选择性,因为降低心肌收缩所需的剂量远高于增加冠状动脉血流量所需的剂量。此外,尼群地平可抑制氯化钾、乙酰胆碱、组胺、去甲肾上腺素、5 - 羟色胺和前列腺素F2α诱导的猪冠状动脉收缩,以及3,4 - 二氨基吡啶诱导的犬冠状动脉节律性收缩。在离体兔主动脉制剂中,尼群地平强烈抑制氯化钾诱导的收缩,但不抑制去氧肾上腺素诱导的收缩。尼群地平的这些作用与硝苯地平的作用几乎相似。提示尼群地平可降低后负荷(血压),增加心脏血流量和氧供应,并抑制冠状动脉痉挛,这是由于其钙拮抗作用所致。尼群地平可能对缺血性心脏病的治疗有用。