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Am J Physiol Heart Circ Physiol 276: H1664-H1671, 1999;
0363-6135/99 $5.00
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Vol. 276, Issue 5, H1664-H1671, May 1999

Effects of aminopeptidase P inhibition on kinin-mediated vasodepressor responses

Shin-Ichi Kitamura1, Luis A. Carbini2, William H. Simmons3, and A. Guillermo Scicli2

1 Hypertension and Vascular Research Division and 2 Eye Care Services Research, Henry Ford Hospital, Detroit, Michigan 48202; and 3 Department of Molecular and Cellular Biochemistry, Loyola University Chicago, Maywood, Illinois 60153

We studied in anesthetized rats whether aminopeptidase P (AMP) may be involved in bradykinin (BK) metabolism and responses. For this we inhibited AMP with the specific inhibitor apstatin (Aps). Studies were done with Aps alone or together with the angiotensin-converting enzyme inhibitor lisinopril (Lis). Aps increased the vasodepressor response to an intravenous bolus of BK (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 into 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 ng · kg-1 · min-1 for 5 min), Aps increased plasma BK (in pg/ml): control, 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 Lis were greater than Lis alone (P < 0.01). Hoe-140, a BK B2-receptor antagonist, abolished the difference. We concluded that in the rat AMP contributes to regulation of BK metabolism and responses.

bradykinin; angiotensin-converting enzyme; kininases; blood pressure


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