The loop diuretic torasemide interferes with endothelin-1 actions in the aorta of hypertensive rats.
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.
Fortuño
A
A
Division of Cardiovascular Pathophysiology, School of Medicine, University of Navarra, Pamplona, Spain.
Muñiz
P
P
Zalba
G
G
Fortuño
M A
MA
Díez
J
J
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D000077300:Bosentan; D002118:Calcium / Q000378:metabolism; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D004232:Diuretics / Q000494:pharmacology*; D019332:Endothelin-1 / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology; D005665:Furosemide / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D051381:Rats; D011918:Rats, Inbred SHR; D013449:Sulfonamides / Q000494:pharmacology*; D000077786:Torsemide; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D000959:Antihypertensive Agents; D018118:Chloride Channels; D004232:Diuretics; D019332:Endothelin-1; D013449:Sulfonamides; D062367:ortho-Aminobenzoates; D005665:Furosemide; C001209:fenamic acid; D000077300:Bosentan; D002118:Calcium; D000077786:Torsemide