Prados P, Santa T, Homma H, Doi H, Narita H, Del Castillo B, Martin M A, Imai K
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Biol Pharm Bull. 1997 Apr;20(4):341-4. doi: 10.1248/bpb.20.341.
Two types of calcium antagonists, diltiazem and nicardipine, were separately infused in 23-28 week-old spontaneously hypertensive (SHR) and age-matched normotensive Wistar-Kyoto (WKY) rats (under sodium thiobutabarbital anesthesia and ventilation, n = 4) through the left femoral vein, resulting in the reduction of blood pressure. In each rat, mean arterial blood pressure, heart rate and the concentration of plasma catecholamines (CAs), norepinephrine (NE) and epinephrine (E), were concomitantly determined and the correlations between these three values were studied for each calcium antagonist. Plasma concentration of CAs were measured in blood samples collected during the infusion from the right femoral artery of each rat by the automatic sensitive and selective detection system. The reduction of blood pressure induced by the calcium antagonists brought about an increase in plasma CAs levels. The blood pressure correlated well with the logarithm of plasma NE and E concentration and the relations were expressed as Y = -alpha log(X)+m (Y, blood pressure; X, concentration of plasma NE or E; alpha, slope; and m, intercept). The alpha s of SHR rats were greater than those of WKY rats for the calcium antagonists employed, meaning that the increment of plasma CAs responding to a decrease in blood pressure was smaller in SHR than in WKY rats. It was concluded that the contribution of the sympathetic nervous system to maintaining blood pressure reduced by diltiazem and nicardipine is less in SHR than in WKY rats.
将两种钙拮抗剂地尔硫卓和尼卡地平分别经左股静脉注入23 - 28周龄的自发性高血压大鼠(SHR)和年龄匹配的血压正常的Wistar - Kyoto大鼠(WKY)(在硫喷妥钠麻醉和通气条件下,每组n = 4),导致血压降低。在每只大鼠中,同时测定平均动脉血压、心率以及血浆儿茶酚胺(CAs)、去甲肾上腺素(NE)和肾上腺素(E)的浓度,并研究每种钙拮抗剂作用下这三个值之间的相关性。通过自动灵敏和选择性检测系统,对每组大鼠在输注过程中从右股动脉采集的血样进行血浆CAs浓度测定。钙拮抗剂引起的血压降低导致血浆CAs水平升高。血压与血浆NE和E浓度的对数呈良好相关性,其关系表示为Y = -αlog(X)+m(Y为血压;X为血浆NE或E浓度;α为斜率;m为截距)。对于所用的钙拮抗剂,SHR大鼠的α值大于WKY大鼠,这意味着SHR大鼠中因血压降低而引起的血浆CAs增量小于WKY大鼠。得出的结论是,在SHR大鼠中,地尔硫卓和尼卡地平降低血压时,交感神经系统对维持血压的贡献小于WKY大鼠。