| 11369815 |
Fortuno A, Muniz P, Zalba G, Fortuno MA, Diez J: The loop diuretic torasemide interferes with endothelin-1 actions in the aorta of hypertensive rats. Nephrol Dial Transplant. 2001;16 Suppl 1:18-21.
BACKGROUND: The direct effects of torasemide and furosemide on vasoconstriction and increases in intracellular free calcium concentration ([Ca (2+)] i) induced by endothelin-1 (ET-1) were investigated in the aorta of spontaneously hypertensive rats (SHR). METHODS: Vascular responses were assessed in endothelium-denuded aortic rings using an organ bath system. Changes of [Ca (2+)] i in cultured vascular smooth muscle cells (VSMCs) were assessed using fura-2 methodology. RESULTS: ET-1-induced vasoconstriction was reduced in a dose-dependent way by torasemide and furosemide (IC (50) values: 4.3+/-1.4x10 (-5) and 9.8+/-5.6 x10 (-5) M, respectively). The ET-1-induced biphasic [Ca (2+)] i increase was blocked by torasemide (IC (50)=2.0+/-0.2x10 (-8) and 2.7+/-0.6x10 (-6) M, respectively). Furosemide inhibited the initial rise in [Ca (2+)] i induced by ET-1, with no effect on the second rise. The specific chloride (Cl (-)) channel blocker diphenylamine-2-carboxylate inhibits both ET-1-induced responses in VSMCs (IC (50)=8.0+/-0.3x10 (-9) and 2.5+/-0.7x10 (-7) M, respectively). CONCLUSIONS: These results suggest that the ability of loop diuretics to interfere with the vascular actions of ET-1 may involve different molecular mechanisms. The ability of torasemide to block the vasoconstrictive action of ET-1 could include an inhibitory action on Cl (-) channels. |
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