Diuretic and cardiovascular effects of furosemide in rats

Dose-response relationships of furosemide to its diuretic and cardiovascular actions and its effects on plasma renin activity (PRA) were evaluated in unanesthetized rats. A dose of 1 mg'kh-1 i.v. induced a small diuretic effect with no change in PRA. Furosemide at 5 mg'kg-1 provoked a clear diuretic effect (about 75) of the maximal effect) accompanied by a 20-25% plasma volume deficit but by only a twofold rise in PRA. Higher doses (10 and 40 mg.kg-1) induced a somewhat larger diuresis without further increases in plasma volume deficit or in PRA. Compared with the marked diuretic effect and plasma volume deficit, water intake increased only slightly (2 mL compared with the diuresis of 10 mL). Furosemide did not induce significant changes in blood pressure and heart rate, but it did alter the renin dependency of the blood pressure as assessed by Saralasin. These results indicate that furosemide has a steep dose-response curve for its effect on plasma volume and PRA; the relation is somewhat less steep for the diuretic action. Considering the large diuresis and plasma volume deficit, the changes in PRA and water intake induced by furosemide appear inappropriately small and suggest an inhibitory effect of furosemide on these parameters.