Enhanced contractility of the rat stomach during suppression of angiotensin converting enzyme by captopril in vitro

Abstract

Intragastric pressure (IGP) was used as an index, of the effect of serosal application of captopril (SQ 14,225; d‐3‐mercapto‐2‐methylpropanoyl‐l‐proline) on the contractility of rat stomach in vitro. Captopril, at concentrations > 0.3 μm, enhanced the spontaneous gastric motility (GM) in a concentration‐dependent manner whereas concentrations < 0.3 μm selectively potentiated 4 nm bradykinin (BK)‐evoked gastric contractions without significantly affecting the spontaneous GM. The kallikrein inhibitor, aprotinin (100 u ml−1), markedly antagonized the enhanced GM to 1.4 μm captopril and BK (4 nm)‐evoked contractions, without affecting the contractions evoked by angiotensin 1 (10 nm) and acetylcholine (0.4 μm). The angiotensin II antagonist, saralasin (50 μm) failed to mimic aprotinin. The enhanced GM to captopril was markedly inhibited by tetrodotoxin (1 μm), and partially inhibited by atropine (1 μm). These results indicate that in vitro, captopril (> 0.3 μm) enhances gastric contractility through kininase/ACE inhibitory action, presumably by increasing the concentration of undegraded tissue kinins and substance P. This motor response seems to be predominantly due to activation of the cholinergic neurones but non‐cholinergic excitatory neurones are also involved. 1991 British Pharmacological Society