Segmental nephron function in rats treated with aprotinin, an inhibitor of kallikrein.

The effects on kidney function of aprotinin, an inhibitor of kallikrein and other serine proteinases, were investigated in rats made diuretic by infusion of 0.9% saline. Late proximal, early distal and late distal tubular fluid samples were collected before and after aprotinin administration (20,000 kallikrein I.U./kg b.wt. i.v.). Glomerular filtration rate and urinary excretion of solute and water were assessed simultaneously. Aprotinin did not alter blood pressure or glomerular filtration rate, but reduced urine flow from 23.8 +/- 4.5 to 16.4 +/- 3.4 microliter min-1 100 g-1 (P less than .05) and urinary kinin excretion from 23.5 +/- 3.2 to 10.8 +/- 1.9 pg min-1 100 g-1 (P less than .01). Aprotinin increased the tubular fluid to plasma inulin concentration ratio at late distal tubule puncture site, but not at late proximal or early distal tubule collection sites. Estimates of fluid reabsorption in the distal convoluted tubule, expressed as a percentage of glomerular filtration rate, as a percentage of delivery to this nephron segment or as net volume transported, increased after the administration of aprotinin by 22, 24 and 23% (P less than .05), respectively. In contrast, aprotinin did not alter the estimates of fluid reabsorption in the proximal convoluted tubule, the loop of Henle or the collecting tubule. We conclude that the antidiuretic effect of aprotinin in saline-expanded rats is related to selective augmentation of fluid reabsorption in the distal convoluted tubule. This effect of aprotinin may be the expression of reduced renal kinin levels, inhibition of serine proteases other than kallikrein or other unrecognized properties of the agent.