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哇巴因诱导自发性高血压大鼠主动脉收缩的钙依赖性

Calcium dependence of ouabain-induced contraction in aortas from spontaneously hypertensive rats.

作者信息

Shibata R, Morita S, Nagai K, Miyata S, Iwasaki T

机构信息

1st Department of Internal Medicine, Hyogo College of Medicine, Japan.

出版信息

Eur J Pharmacol. 1990 Nov 6;190(1-2):147-57. doi: 10.1016/0014-2999(90)94121-d.

Abstract

The calcium sensitivity of ouabain-induced contractions of aortic strips from spontaneously hypertensive rat (SHR) was examined using several drugs which affect Na+ and Ca2+ movements across the cell membrane, and the results were compared with those obtained with age-matched Wistar-Kyoto rat (WKY). The Ca2+ concentration-response curves (10(-3) M ouabain-treated preparations) made with aortic strips from SHR lay to the left of those made with aortic strips from WKY (Ca EC50 values: SHR, 0.51 +/- 0.16 mM, n = 6; WKY, 1.23 +/- 0.41 mM, n = 7; P less than 0.05). Amiloride (a Na+ entry blocker) and nifedipine (a Ca2+ entry blocker) attenuated the sensitivity to Ca2+ of SHR and WKY aortic strips. With 2 x 10(-4) M amiloride, WKY vessels showed a 1.3-fold increase in the Ca EC50 value and SHR a 2.1-fold increase. With 10(-6) M nifedipine. WKY vessels showed a 1.1-fold increase in the Ca EC50 value and SHR a 1.5-fold increase. Addition of monensin (Na ionophore) produced a dose-dependent potentiation in ouabain-treated aorta from WKY, but not in ouabain-treated aorta from SHR. Addition of 1.5 x 10(-5) M A23187 (Ca ionophore) eliminated the difference between the Ca2(+)-induced contractions in aortas from SHR and WKY. These results suggest that enhancement of Ca2+ influx by Na(+)-Ca2+ exchange and/or voltage-dependent Ca2+ channels in vascular smooth muscle cell membranes may be an important factor in the difference between ouabain-induced contractions in aorta from SHR and WKY.

摘要

使用几种影响钠和钙跨细胞膜转运的药物,检测了哇巴因诱导的自发性高血压大鼠(SHR)主动脉条收缩的钙敏感性,并将结果与年龄匹配的Wistar-Kyoto大鼠(WKY)的结果进行了比较。用SHR主动脉条绘制的钙浓度-反应曲线(用10⁻³ M哇巴因处理的标本)位于用WKY主动脉条绘制的曲线左侧(钙EC50值:SHR,0.51±0.16 mM,n = 6;WKY,1.23±0.41 mM,n = 7;P<0.05)。氨氯地平(一种钠内流阻滞剂)和硝苯地平(一种钙内流阻滞剂)减弱了SHR和WKY主动脉条对钙的敏感性。使用2×10⁻⁴ M氨氯地平,WKY血管的钙EC50值增加1.3倍,SHR增加2.1倍。使用10⁻⁶ M硝苯地平,WKY血管的钙EC50值增加1.1倍,SHR增加1.5倍。添加莫能菌素(钠离子载体)使WKY经哇巴因处理的主动脉产生剂量依赖性增强作用,但对SHR经哇巴因处理的主动脉无此作用。添加1.5×10⁻⁵ M A23187(钙离子载体)消除了SHR和WKY主动脉中钙诱导收缩之间的差异。这些结果表明,血管平滑肌细胞膜中钠-钙交换和/或电压依赖性钙通道介导的钙内流增强可能是SHR和WKY主动脉中哇巴因诱导收缩差异的一个重要因素。

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