Shimamura K, Sekiguchi F, Matsuda K, Yamamoto K, Tanaka S, Sunano S, Shibutani T, Hashimoto H, Tanaka M
Research Institute of Hypertension, Kinki University, Osaka-Sayama, Osaka, Japan.
Eur J Pharmacol. 1998 Mar 5;344(2-3):161-8. doi: 10.1016/s0014-2999(97)01573-2.
The effects of chronic treatment of stroke-prone spontaneously hypertensive rats (SHRSP) with carvedilol, an antihypertensive agent which has both alpha- and beta-adrenoceptor-blocking actions, on membrane potential and relaxation of mesenteric resistant artery were studied. Five-week old SHRSP were treated with carvedilol for three months. At 16 weeks, the resting membrane potential of arteries from carvedilol-treated SHRSP was more negative than that of arteries from untreated SHRSP. The magnitude of acetylcholine-induced hyperpolarization in arteries from carvedilol-treated SHRSP was not different from that of arteries from untreated SHRSP. In the presence of noradrenaline, the membrane potential of arteries from carvedilol-treated SHRSP was more negative than that of arteries from untreated SHRSP. The membrane potential of arteries from carvedilol-treated SHRSP in the presence of noradrenaline and acetylcholine was more negative than that of arteries from untreated SHRSP. The acetylcholine-induced relaxation in noradrenaline-precontracted preparations from carvedilol-treated SHRSP was greater than that in preparations from untreated SHRSP and was smaller than that in preparations from Wistar Kyoto rats. Scanning electronmicroscopy showed that carvedilol-treatment decreased the structural abnormalities of the endothelium of arteries from SHRSP. These results indicate that chronic carvedilol treatment made the membrane potential of smooth muscle more negative and improved endothelial function in the mesenteric artery of SHRSP, which may contribute to the antihypertensive effect of carvedilol.
研究了用卡维地洛(一种兼具α和β肾上腺素能受体阻断作用的抗高血压药物)长期治疗易中风自发性高血压大鼠(SHRSP)对肠系膜阻力动脉膜电位和舒张功能的影响。5周龄的SHRSP用卡维地洛治疗3个月。在16周时,卡维地洛治疗的SHRSP的动脉静息膜电位比未治疗的SHRSP的动脉更负。卡维地洛治疗的SHRSP的动脉中乙酰胆碱诱导的超极化幅度与未治疗的SHRSP的动脉无差异。在去甲肾上腺素存在的情况下,卡维地洛治疗的SHRSP的动脉膜电位比未治疗的SHRSP的动脉更负。在去甲肾上腺素和乙酰胆碱存在的情况下,卡维地洛治疗的SHRSP的动脉膜电位比未治疗的SHRSP的动脉更负。卡维地洛治疗的SHRSP的去甲肾上腺素预收缩制剂中乙酰胆碱诱导的舒张大于未治疗的SHRSP的制剂,且小于Wistar Kyoto大鼠的制剂。扫描电子显微镜显示,卡维地洛治疗减少了SHRSP动脉内皮的结构异常。这些结果表明,长期卡维地洛治疗使平滑肌膜电位更负,并改善了SHRSP肠系膜动脉的内皮功能,这可能有助于卡维地洛的抗高血压作用。