Potentiation of the diuretic and natriuretic effect of furosemide by the calcium antagonist nifedipine.

The renal excretory function was studied in rats under control conditions, after treatment with nifedipine, with furosemide and combined treatment with nifedipine and furosemide. The experimental animals were investigated in metabolic cages. Spontaneously excreted urine was collected for 6 h (under control conditions and when nifedipine was applied) and for two hours in the experiments with furosemide treatment. The diuresis, the excretion of sodium, potassium, chlorine, creatinine and the total amount of osmotically active substances were studied. Blood samples were taken from the heart under nembutal anaesthesia. The clearances and the excretory fractions of the substances tested were determined. The glomerular filtration was determined by the clearance of the endogenous creatinine. The blood pressure in the tail artery was measured in control experiments. Increased diuresis was observed after treatment with nifedipine, without substantial changes in the sodium, chlorine, potassium and total osmotic excretion. When furosemide was applied after pretreatment with nifedipine, the diuresis was by 33 per cent higher than when only furosemide was applied (p less than 0.01), sodium excretion was by 40% higher (p less than 0.01) and that of chlorine--by 16.9% (p less than 0.01). Potassium excretion remained unchanged. The results of the excretory fractions and of the clearances of the substances studied support the evidence about potentiation of the natriuretic and chlorouretic effect of furosemide under the effect of nifedipine. The concentrating function of the kidney, determined through the clearance parameter Cosm/TcH2O manifested an additional limitation under the effect of nifedipine.