Torasemide Inhibits Angiotensin II–Induced Vasoconstriction and Intracellular Calcium Increase in the Aorta of Spontaneously Hypertensive Rats

摘要

Abstract —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 (pD2=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 μmol/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 (pD2=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.