The effect of aprotinin (a serine protease inhibitor) on renal function and renin release

We studied the effect of aprotinin, a reversible inhibitor of kallikrein and other serine proteases, upon urinary kallikrein and kinin excretion, renal function and hemodynamics, blood pressure, and plasma renin activity (PRA). When aprotinin was administered to anesthetized rats at 10,000 KIU/kg as a bolus, and at 1000 KIU/kg/min infusion for 60 minutes, urinary kininogenase activity and immunoreactive kallikrein, kinins, sodium, potassium, and water excretion, and PRA decreased significantly. Aprotinin also caused a 36% decrease (p less than 0.001) in renal blood flow (RBF), and a 37% decrease (p less than 0.001) in glomerular filtration rate (GFR), although neither blood pressure nor cardiac output changed. The effect of aprotinin on PRA was further studied in conscious rats before and after stimulation of renin release by isoproterenol or furosemide. Aprotinin (5,000 KIU/kg bolus and 1000 KIU/kg/min infusion for 60 minutes) did not alter basal or isoproterenol-stimulated PRA, but it blunted the increase in PRA as stimulated by furosemide. Aprotinin at a higher dose (20,000 KIU/kg bolus and 5000 KIU/kg/min infusion for 60 minutes) significantly lowered blood pressure and increased hematocrit and PRA. These effects may be due to inhibition of serine protease(s) or to other as yet unrecognized properties of this peptide resulting from its highly cationic nature. In conclusion, aprotinin at a low dose decreased kallikrein, kinin, sodium, and water excretion. These decreases may be due to the inhibition of kallikrein and/or other serine proteases or may be secondary to the renal hemodynamic changes.(ABSTRACT TRUNCATED AT 250 WORDS)