Torasemide inhibits angiotensin II-induced vasoconstriction and intracellular calcium increase in the aorta of spontaneously hypertensive rats

Torasemide is a loop diuretic that is effective at low once-daily doses in the treatment of arterial hypertension. Because its antihypertensive mechan ism of action may not be :based entirely on the elimination of salt and wat er,from the body, a vasodilator effect of this drug can be considered. In t he present study, the ability of different concentrations Of torasemide to modify angiotensin II (Ang II)-induced vascular responses was examined, wit h 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 analysi s in cultured vascular smooth muscle cells (VSMCs) from spontaneously hyper tensive rats. A dose;response curve to Ang II was plotted for cumulative co ncentrations (from 10(-9) to 10(-6) mol/L) in endothelium-denuded aortic ri ngs (pD(2) = 7.5+/-0.3). Isometric contraction induced by a submaximal conc entration of Ang II (10(-7) mol/L) was reduced in a dose-dependent way by t orasemide (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) wa s blocked by torasemide (IC50 = 0.5+/-0.3 nmol/L). Our findings suggest tha t torasemide blocks the vasoconstrictor action of Ang II in vitro. This act ion can be related to the ability of torasemide to block the increase of [C a2+](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.