Paciorek P M, Burden D T, Burke Y M, Cowlrick I S, Perkins R S, Taylor J C, Waterfall J F
Department of Biology, Roche Products Limited, Hertfordshire, England.
J Cardiovasc Pharmacol. 1990 Feb;15(2):188-97. doi: 10.1097/00005344-199002000-00003.
The present study compares the effects of Ro 31-6930, a novel potassium channel opener, with those of cromakalim and nitrendipine on blood pressure and other haemodynamic parameters. In conscious, spontaneously hypertensive rats (SHR) the oral dose of Ro 31-6930 for lowering blood pressure was 10 times lower than that of cromakalim and some 100 times lower than that of nitrendipine. In addition, the duration of antihypertensive activity of Ro 31-6930 was longer than that of cromakalim or nitrendipine. The tachycardia evoked by Ro 31-6930 and cromakalim was of shorter duration than the antihypertensive effect of either agent. In a repeat, once daily dosing experiment no tolerance was observed to the antihypertensive effect of Ro 31-6930 over a 22-day period. In conscious normotensive cats Ro 31-6930 was 10 times more potent than cromakalim and 1,000 times more potent than nitrendipine in reducing blood pressure. The duration of hypotensive activity was in excess of 5 h for each agent. In anaesthetised dogs all three agents reduced mean arterial pressure (MAP) and total peripheral resistance (TPR), while increasing cardiac output (CO) via a rise in stroke volume (SV). Both Ro 31-6930 and cromakalim significantly reduced femoral (FVR) and mesenteric vascular resistances (MVR), while only cromakalim reduced renal vascular resistance (RVR). Ro 31-6930 is a potent new antihypertensive agent that compares favourably with cromakalim and nitrendipine.
本研究比较了新型钾通道开放剂Ro 31-6930与克罗卡林和尼群地平对血压及其他血流动力学参数的影响。在清醒的自发性高血压大鼠（SHR）中，Ro 31-6930降低血压的口服剂量比克罗卡林低10倍，比尼群地平低约100倍。此外，Ro 31-6930的降压活性持续时间比克罗卡林或尼群地平更长。Ro 31-6930和克罗卡林引起的心动过速持续时间比这两种药物中任何一种的降压作用持续时间都短。在重复的每日一次给药实验中，在22天的时间内未观察到对Ro 31-6930降压作用的耐受性。在清醒的正常血压猫中，Ro 31-6930在降低血压方面比克罗卡林强10倍，比尼群地平强1000倍。每种药物的降压活性持续时间超过5小时。在麻醉犬中，所有三种药物均降低平均动脉压（MAP）和总外周阻力（TPR），同时通过增加每搏量（SV）来增加心输出量（CO）。Ro 31-6930和克罗卡林均显著降低股动脉（FVR）和肠系膜血管阻力（MVR），而只有克罗卡林降低肾血管阻力（RVR）。Ro 31-6930是一种有效的新型降压药，与克罗卡林和尼群地平相比具有优势。
