Lappe R W, Todt J A, Wendt R L
Division of Experimental Therapeutics, Wyeth Laboratories, Inc., Philadelphia, PA 19101.
Am J Hypertens. 1988 Jan;1(1):47-9. doi: 10.1093/ajh/1.1.47.
Calcitonin gene-related peptide (CGRP) is a potent peripheral vasodilator. In the present study, the cardiovascular effects of centrally administered CGRP were examined in conscious, normotensive rats. The rats were chronically instrumented with miniaturized pulsed Doppler flow probes to allow measurement of regional blood flow in the conscious animals. Injection of increasing doses of CGRP (0.3 to 3.0 micrograms/kg) in the lateral cerebroventricles transiently increased arterial pressure (maximal change = 13 +/- 3 mm Hg) and markedly increased heart rate (maximal increase = 88 +/- 10 b/min). The heart rate response was sustained over a period of 20 to 30 minutes. Central CGRP decreased hindquarter vascular resistance but had no effect on renal or mesenteric vascular resistances. In contrast, intravenous injections of CGRP reduced arterial pressure and renal, mesenteric, and hindquarter vascular resistances. The tachycardia response to central CGRP was attenuated by pretreatment with propranolol or hexamethonium, indicating that the heart rate response was mediated, in part, through increases in cardiac sympathetic tone. These data indicate that central CGRP may alter cardiovascular function through alterations in sympathetic outflow.
降钙素基因相关肽(CGRP)是一种强效的外周血管扩张剂。在本研究中,对清醒的正常血压大鼠进行了中枢给予CGRP的心血管效应研究。这些大鼠长期植入小型化脉冲多普勒血流探头,以便在清醒动物中测量局部血流。向侧脑室注射递增剂量的CGRP(0.3至3.0微克/千克)可使动脉压短暂升高(最大变化 = 13±3毫米汞柱),并显著增加心率(最大增加 = 88±10次/分钟)。心率反应在20至30分钟内持续存在。中枢给予CGRP可降低后肢血管阻力,但对肾或肠系膜血管阻力无影响。相比之下,静脉注射CGRP可降低动脉压以及肾、肠系膜和后肢血管阻力。用普萘洛尔或六甲铵预处理可减弱对中枢给予CGRP的心动过速反应,表明心率反应部分是通过心脏交感神经张力增加介导的。这些数据表明,中枢CGRP可能通过改变交感神经输出而改变心血管功能。