Effects of aminopeptidase P inhibition on kinin-mediated vasodepressor responses

We studied in anesthetized rats whether aminopeptidase P (AMP) may be invol ved in bradykinin (BK) metabolism and responses. For this we inhibited AMP with the specific inhibitor apstatin (Aps). Studies were done with Aps alon e or together with the angiotensin-converting enzyme inhibitor lisinopril ( Lis). Aps increased the vasodepressor response to an intravenous bolus of B K (400 ng/kg): vehicle, -3.0 +/- 0.7 mmHg; Aps, -7.8 +/- 0.7 mmHg (P < 0.01 vs. vehicle); Lis, -23.8 +/- 1.8 mmHg; Aps + Lis, -37.5 +/- 1.9 mmHg (P < 0.01 vs. Lis). Aps did not affect the vasodepressor response to BK given in to the descending aorta. Plasma BK increased only in Aps + Lis-treated rats (in pg/ml): control, 48.0 +/- 1.4; Lis, 57.5 +/- 7.6; Aps + Lis, 121.8 +/- 30.6 (P < 0.05 vs, control or Lis), whereas in rats infused with BK (400 n g . kg(-1) . min(-1) for 5 min), Aps increased plasma BK tin pg/ml): contro l, 51.9 +/- 2.5; Aps, 83.5 +/- 20.5; Lis, 725 +/- 225; Aps + Lis, 1,668 +/- 318 (P < 0.05, Aps vs, control and Lis vs. Aps + Lis). In rats with aortic coarctation hypertension, the acute antihypertensive effects of Aps plus L is were greater than Lis alone (P < 0.01). Hoe-140, a BK B-2-receptor antag onist, abolished the difference. We concluded that in the rat AMP contribut es to regulation of BK metabolism and responses.