Prados P, Santa T, Fukushima T, Homma H, Kasai C, Martin M A, del Castillo B, Imai K
Department of Bio-Analytical Chemistry, Graduate Schol of Pharmaceutical Sciences, The University of Tokyo, Japan.
Hypertens Res. 1998 Sep;21(3):147-53. doi: 10.1291/hypres.21.147.
Nicardipine, a dihydropyridine type calcium channel blocker, was infused into 4-, 6-, and 23-wk-old spontaneously hypertensive (SH) 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 variables were studied. During the infusion of nicardipine, the plasma concentration of CAs was measured with an automatic detection system in blood samples collected from the right femoral artery of each rat. The reduction in blood pressure induced by nicardipine brought about an increase in plasma CA levels. The blood pressure correlated well with the logarithm of plasma NE or E concentration according to the formula Y= -alpha log (X) + m (Y, blood pressure; X, concentration of plasma NE or E; a, slope; and m, intercept). The slopes (as) of 6-wk-old and 23-wk-old SH rats were significantly greater than those of aged-matched WKY rats, meaning that the increment in plasma CAs in response to a decrease in blood pressure was smaller in SH than in WKY rats of similar ages. However, no significant differences were found between the as of 4-wk-old SH and WKY rats. We conclude that the increment in the baroreflex-mediated sympathetic activity in response to a drop in blood pressure induced by nicardipine is similar or greater in prehypertensive SH than in normotensive WKY 4-wk-old rats, while the increment becomes smaller in SH rats with the onset of hypertension (6-wk-old rats), and is much less in fully hypertensive adult (23-wk-old) SH rats than in age-matched WKY rats. On the basis of these findings and previous data obtained by neurography, we conclude that plasma CAs can be used to evaluate baroreflex-mediated sympathetic activity countering the blood pressure reduction caused by calcium antagonists.
尼卡地平是一种二氢吡啶类钙通道阻滞剂，通过左股静脉将其注入4周龄、6周龄和23周龄的自发性高血压（SH）大鼠以及年龄匹配的正常血压Wistar - Kyoto（WKY）大鼠体内（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，并研究这三个变量之间的相关性。在输注尼卡地平期间，使用自动检测系统测定从每只大鼠右股动脉采集的血样中的血浆CAs浓度。尼卡地平引起的血压降低导致血浆CA水平升高。根据公式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），血压与血浆NE或E浓度的对数具有良好的相关性。6周龄和23周龄SH大鼠的斜率（αs）显著大于年龄匹配的WKY大鼠，这意味着在血压下降时，SH大鼠血浆CAs的增加幅度小于相似年龄的WKY大鼠。然而，4周龄SH大鼠和WKY大鼠的αs之间未发现显著差异。我们得出结论，对于尼卡地平诱导的血压下降，血压前期SH大鼠压力反射介导的交感神经活动增加幅度与正常血压4周龄WKY大鼠相似或更大，而在高血压发作的SH大鼠（6周龄大鼠）中增加幅度变小，在完全高血压的成年（23周龄）SH大鼠中增加幅度远小于年龄匹配的WKY大鼠。基于这些发现以及先前通过神经造影获得的数据，我们得出结论，血浆CAs可用于评估压力反射介导的交感神经活动对钙拮抗剂引起的血压降低的反应。
