Opposing effects of captopril and aprotinin on tubuloglomerular feedback responses

We investigated the effect of two protease inhibitors, captopril and aprotinin, on tubuloglomerular feedback. In anesthetized rats, 15 or 25 mg/kg captopril significantly reduced the change of early proximal flow rate achieved by raising loop of Henle perfusion rate from 0 to 40 nl/min. Consistent with this reduction of maximum responses, there was a rise of single nephron glomerular filtration rate from 30.7 +/- 1.15 to 35.0 +/- 0.93 nl/min (P less than 0.01) following 25 mg/kg captopril. Infusion of aprotinin at 40,000 KIU/h produced an increase in maximum feedback responses from 38.2 +/- 1.66 to 56.8 +/- 2.35% (P less than 0.05). Infusion of aprotinin in two different doses (20,000 or 40,000 KIU/h) diminished or prevented the effect of 25 mg/kg captopril on maximum feedback responses. Since the main action of aprotinin is believed to be kallikrein inhibition, our data suggest that the magnitude of feedback responses may be affected by the kallikrein-kinin system and that the action of captopril may be in part mediated by its interference with kinin metabolism.