Inhibition of furosemide-induced increases in plasma renin activity by amiloride

The effect of the potassium-sparing diuretic, amiloride, was studied in conscious rabbits bearing chronic indwelling cannulas to assess whether its reported in vitro kallikrein-inhibiting activity may produce a suppressive effect on furosemide-induced renin secretion similar to that previously demonstrated with another kallikrein inhibitor, aprotinin. Furosemide elicited a rapid and persistent rise in plasma renin activity (PRA), but pretreatment of the same rabbits with a 15-minute intravenous infusion of amiloride, which amounted to 1 mg/kg and commenced at 30 minutes before furosemide, completely prevented this rise. Amiloride also prevented furosemide-induced kaliuresis without an attenuation of the diuretic or natriuretic response and did not alter plasma potassium concentration in the absence of any change in external potassium balance, indicating that suppression of the PRA response is due neither to prevention of extracellular fluid volume contraction nor to the known suppressive effect of hyperkalemia. Mean arterial pressure tended to fall slightly but not significantly with or without amiloride pretreatment. On the basis of these findings and those of our antecedent study with aprotinin, we conclude that the striking similarity between the suppressive effects of two dissimilar inhibitors of kallikrein on pharmacologically evoked renin secretion is consistent with the hypothesis that renal kallikrein participates in the mechanism of renin secretion in vivo.