DIURETIC ACTION OF THE NOVEL LOOP DIURETIC TORASEMIDE IN THE PRESENCE OF ANGIOTENSIN-II OR ENDOTHELIN-1 IN ANESTHETIZED DOGS

The effects of torasemide (0.1 and 1 mg kg-1, i.v.) and furosemide (3 mg kg-1) on renal haemodynamics and excretory responses in the presence of angiotensin II and endothelin-1 was examined in anaesthetized dogs. Angiotensin II or endothelin-1 was continuously infused into the renal artery throughout the experiment and a bolus of torasemide or furosemide was injected into the bracheal vein. Continuous intrarenal arterial (i.r.a.) infusion of angiotensin II, at a dose of 5 ng kg-1 min-1, increased renal vascular resistance (RVR) and decreased renal blood flow (RBF) and glomerular filtration rate (GFR), but had no effect on systemic mean arterial pressure (MAP). Urinary excretion of sodium (U(Na)V) and urine flow (UF) were significantly decreased during angiotensin II infusion. Intravenous injections of torasemide in the presence of angiotensin II caused a dose-dependent increase in UF, U(Na)V and urinary excretion of potassium (U(K)V), while a decrease in RVR was accompanied by an increase in RBF. U(K)V was greater in the furosemide group than in the torasemide group, despite both groups having the same degree of aquaresis and natriuresis. Continuous i.r.a. infusion of endothelin-1, 1.5 ng kg-1 min-1, produced effects similar to those of angiotensin II on renal haemodynamics; however, the onset of action was extremely slow compared with the effects produced by angiotensin II. Endothelin-1 caused a significant decrease in UF, U(Na)V and U(K)V only at a later period, despite a relatively early depression of renal haemodynamics. Torasemide and furosemide also produced a sufficient diuretic action in this model. Overall, kaliuresis was greater in the furosemide group than in the torasemide group. The present study demonstrates that torasemide exhibited a significant diuretic action in the angiotensin II- or endothelin-1-induced renal impairment model, with less kaliuresis than furosemide at a concentration which caused the same degree of natriuresis.