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

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 1999-07, Vol.34 (1), p.138-143
• Main Authors: Fortuno, Ana, Muniz, Paula, Ravassa, Susana, Rodriguez, Jose Antonio, Fortuno, M Antonia, Zalba, Guillermo, Diez, Javier
• Format: Article
• Language: English
• Subjects: Angiotensin II - pharmacology; Animals; Antihypertensive agents; Antihypertensive Agents - pharmacology; Aorta - drug effects; Aorta - metabolism; Biological and medical sciences; Biphenyl Compounds - pharmacology; Calcium - metabolism; Cardiovascular system; Cells, Cultured; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; Furosemide - pharmacology; Hypertension - metabolism; Hypertension - physiopathology; Intracellular Membranes - metabolism; Irbesartan; Male; Medical sciences; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - pathology; Pharmacology. Drug treatments; Rats; Rats, Inbred SHR; Sulfonamides - pharmacology; Tetrazoles - pharmacology; Torsemide; Vasoconstriction - drug effects
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.hyp.34.1.138

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 ([Ca]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 to 10 mol/L) in endothelium-denuded aortic rings (pD2=7.5 +/- 0.3). Isometric contraction induced by a submaximal concentration of Ang II (10 mol/L) was reduced in a dose-dependent way by torasemide (IC50=0.5 +/- 0.04 [micro sign]mol/L). Incubation of VSMCs with different concentrations of Ang II (from 10 to 10 mol/L) resulted in a dose-dependent rise of [Ca]i (pD2=7.5 +/- 0.3). The stimulatory effect of [Ca]i induced by a submaximal concentration of Ang II (10 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 [Ca]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. (Hypertension. 1999;34:138-143.)