A quantitative method of evaluating the diuretic response to furosemide in rats

Furosemide effects are usually evaluated by measuring the urinary excretion rate of Na+ (UVNa) in humans. In the present study, however, UVNa showed a nonlinear relationship with urine flow rate after intravenous injection of furosemide in rats. In contrast, when the urinary excretion rate of (Na+ + K+) (UVNa + K) was plotted against the urine flow rate, a linear regression line was observed, with small interindividual variations in normal rats and in rats with uranyl nitrate-induced acute renal failure (ARF). Piretanide, a loop diuretic, also showed a similar relationship, while other types of diuretics revealed different slope values for the relationship. Although the urinary excretion rate of Cl- (UVCl) vs UVNa + K is expected to show a linear relationship in normal rats, the correlation coefficient of the linear regression line was smaller than that of the urine flow rate vs UVNa + K. Further, the slope of UVCl vs UVNa + K was slightly different in ARF rats. Therefore, UVNa + K provides a better quantitative measure of diuretic response to loop diuretics than UVNa or UVCl.