The loop diuretic torasemide interferes with endothelin-1 actions in the aorta of hypertensive rats

Background, The direct effects of torasemide and furosemide ton vasoconstri ction and increases in intracellular free calcium concentration ([Ca2+](i)) induced by endothelin-1 (ET-1) were investigated in the aorta of spontaneo usly hypertensive rats (SHR). Methods, Vascular responses were assessed in endothelium-denuded aortic rin gs using an organ bath system. Changes of [Ca2+](i) in cultured vascular sm ooth 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 (IC50 values: 4.3 +/- 1.4 x 10(-5) and 9.8 +/- 5.6 x 10(-5) M, respectively). The ET-1-induced biphasic [Ca2+](i) increas e was blocked by torasemide (IC50 = 2.0 +/- 0.2 x 10(-8) and 2.7 +/- 0.6 x 10(-6) M, respectively). Furosemide inhibited the initial rise in [Ca2+](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-induce d responses in VSMCs (IC50 = 8.0 +/- 0.3 x 10(-9) and 2.5 +/- 0.7 x 10(-7) M, respectively). Conclusions. These results suggest that the ability of loop diuretics to in terfere with the vascular actions of ET-1 may involve different molecular m echanisms. The ability of torasemide to block the vasoconstrictive action o f ET-1 could include an inhibitory action on Cl- channels.