Torasemide inhibits angiotensin II-induced vasoconstriction and intracellular calcium increase in the aorta of spontaneously hypertensive rats
Torasemide inhibits angiotensin II-induced vasoconstriction and intracellular calcium increase in the aorta of spontaneously hypertensive rats
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DOI：
10.1161/01.hyp.34.1.138
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发表时间：
1999-07-01
期刊：
影响因子：
8.3
通讯作者：
Díez, J
中科院分区：
文献类型：
--
作者：
Fortuño, A;Muñiz, P;Díez, J
托拉塞米是一种环状利尿剂，在治疗动脉高血压时每天一次的低剂量有效。因为其抗高血压的作用机制可能不是：完全基于排出体内的盐分和水分，可以考虑这种药物的血管扩张作用。在本研究中，利用器官浴系统，观察了不同浓度的托拉塞米对血管紧张素II(Ang II)诱导的血管反应的影响。用图像分析技术检测Ang II诱导的自发性高血压大鼠血管平滑肌细胞(VSMCs)内游离钙浓度([Ca~(2+)](I))的升高。血管紧张素Ⅱ对血管紧张素Ⅱ的累积浓度(从10(-9)~10(-6)摩尔/L)绘制成剂量-反应曲线(PD(2)=7.5+/-0.3)。托拉塞米可剂量依赖性地抑制次最大浓度血管紧张素Ⅱ(10(-7)m ol/L)引起的等长收缩(IC_(50)=0.5+/-0.04 m o l/L)。血管紧张素Ⅱ与不同浓度的血管紧张素Ⅱ(10(-10)~10(-6)m ol/L)孵育后，[Ca~(2+)](I)呈剂量依赖性升高(pD(2)=7.5+/-0.3)。托拉塞米(IC_(50)=0.5+/-0.3nmol/L)可阻断次最大浓度血管紧张素Ⅱ(10(-7)m o l/L)对[Ca~(2+)](I)的刺激作用。我们的研究结果表明托拉塞米在体外阻断了血管紧张素II的血管收缩作用。此作用可能与托拉塞米阻断血管紧张素转换酶II诱导的血管内皮细胞内钙离子浓度升高有关。这些作用可能与托拉塞米体内观察到的降压作用有关。
Torasemide is a loop diuretic that is effective at low once-daily doses in the treatment of arterial hypertension. Because its antihypertensive mechanism of action may not be :based entirely on the elimination of salt and water,from the body, a vasodilator effect of this drug can be considered. In the present study, the ability of different concentrations Of torasemide to modify angiotensin II (Ang II)-induced vascular responses was examined, with the use of an organ bath system, in endothelium-denuded aortic rings from spontaneously hypertensive rats. Ang II-induced increases of intracellular free calcium concentration ([Ca2+](i)) were also examined by image analysis in cultured vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats. A dose;response curve to Ang II was plotted for cumulative concentrations (from 10(-9) to 10(-6) mol/L) in endothelium-denuded aortic rings (pD(2) = 7.5+/-0.3). Isometric contraction induced by a submaximal concentration of Ang II (10(-7) mol/L) was reduced in a dose-dependent way by torasemide (IC50 = 0.5+/-0.04 mu mol/L). Incubation of VSMCs with different concentrations of Ang II (from 10(-10) to 10(-6) mol/L) resulted in a dose-dependent rise of [Ca2+](i) (pD(2) = 7.5+/-0.3). The stimulatory effect of [Ca2+](i) induced by a submaximal concentration of Ang II (10(-7) mol/L) was blocked by torasemide (IC50 = 0.5+/-0.3 nmol/L). Our findings suggest that torasemide blocks the vasoconstrictor action of Ang II in vitro. This action can be related to the ability of torasemide to block the increase of [Ca2+](i) induced by Ang II in VSMCs. It is proposed that these actions might be involved in the antihypertensive effect of torasemide observed in vivo.