PHARMACOLOGICAL ACTION OF PHENYLPROPYL]ALANYL]HEXAHYDRO-2-INDOLINECARBOXYLIC ACID (TRANDOLAPRILAT) IN ISOLATED SMOOTH-MUSCLE PREPARATIONS

1. Trandolaprilat was found to inhibit angiotensin I (Ang I)-induced c ontraction of the rat thoracic aorta, and to augment bradykinin(BK)-in duced contraction of the guinea pig ileum. In inhibitory activity (IC5 0) on the Ang I induced contraction of the rat thoracic aorta, trandol aprilat was about 2.4 times as potent as enalaprilat. Concerning the a ugmenting activity (AC50) on bradykinin-induced contraction of the gui nea pig ileum, the activity of trandolaprilat was similar to that of e nalaprilat. 2. Trandolaprilat had no effect on contractions induced by norepinephrine, PGF2alpha, 5-HT or CaCl2 in the thoracic aorta of rat s. 3. Trandolaprilat produced endothelium-dependent relaxation. This r elaxation was inhibited by N(G)-methyl-L-arginine treatment, suggestin g that endothelium-dependent relaxation of trandolaprilat is related t o endothelium-derived-relaxation-factor(EDRF/NO). Like trandolaprilat, captopril also produced endothelium-dependent relaxation, whereas ena laprilat had no effect.