Imai K, Higashidate S, Prados P R, Santa T, Adachi-Akahane S, Nagao T
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Biol Pharm Bull. 1994 Jul;17(7):907-10. doi: 10.1248/bpb.17.907.
Three types of calcium antagonists, diltiazem, verapamil and nicardipine, were separately infused into Sprague-Dawley (SD) rats (under pentobarbital anesthesia n = 5) through the left femoral vein at four different flow rates. Mean arterial blood pressure, heart rate and the concentration of plasma catecholamines (CAs), epinephrine (E), norepinephrine (NE) and dopamine (DA), were measured for each calcium antagonist, and the correlations between them were studied. Blood samples were collected within the infusion from common jugular vein. Plasma concentrations of CAs were determined by a HPLC-ethylenediamine condensation reaction-peroxyoxalate chemiluminescence detection system (HPLC-ED-PO-CL). The plasma concentration of CAs increased corresponding to the blood pressure reduction. The reduction induced by each calcium antagonist correlated with the logarithm of plasma NE concentration. The relation was expressed as Y = -alpha log X+m (Y, blood pressure; X, concentration of plasma NE; alpha, slope; and m, intercept). The correlation coefficients (rs) were -0.950 (diltiazem), -0.975 (verapamil) and -0.978 (nicardipine) (versus -0.734 for control). The alpha for nicardipine (108.4) was greater than those of diltiazem (85.4) and verapamil (80.8) (versus 31.0 for control), meaning that blood pressure reduction was greater in the case of nicardipine than diltiazem and verapamil, with an identical increment of plasma NE concentration. These data indicate that the contribution of the sympathetic nervous system to maintaining blood pressure reduced by nicardipine is less than that observed following the infusion of diltiazem and verapamil. Similar good inverse correlations between blood pressure and the logarithm of plasma concentration of E were observed with the three drugs infused (r = -0.928, -0.966, and -0.948 for diltiazem, verapmil and nicardipine, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
将三种钙拮抗剂，即地尔硫卓、维拉帕米和尼卡地平，分别以四种不同流速通过左股静脉注入处于戊巴比妥麻醉状态的斯普拉格-道利（SD）大鼠（n = 5）体内。针对每种钙拮抗剂测量平均动脉血压、心率以及血浆儿茶酚胺（CA）、肾上腺素（E）、去甲肾上腺素（NE）和多巴胺（DA）的浓度，并研究它们之间的相关性。在输液过程中从颈静脉采集血样。采用高效液相色谱-乙二胺缩合反应-过氧草酸酯化学发光检测系统（HPLC-ED-PO-CL）测定血浆CA浓度。血浆CA浓度随着血压降低而升高。每种钙拮抗剂引起的血压降低与血浆NE浓度的对数相关。该关系表示为Y = -αlogX + m（Y为血压；X为血浆NE浓度；α为斜率；m为截距）。相关系数（rs）分别为-0.950（地尔硫卓）、-0.975（维拉帕米）和-0.978（尼卡地平）（对照组为-0.734）。尼卡地平的α值（108.4）大于地尔硫卓（85.4）和维拉帕米（80.8）（对照组为31.0），这意味着在血浆NE浓度相同增量的情况下，尼卡地平导致的血压降低幅度大于地尔硫卓和维拉帕米。这些数据表明，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注入地尔硫卓和维拉帕米后的情况。在注入这三种药物时，血压与血浆E浓度对数之间也观察到类似良好的负相关（地尔硫卓、维拉帕米和尼卡地平的r分别为-0.928、-0.966和-0.948）。（摘要截短为250字）
