Pharmacological action of (-)-(2S,3aR,7aS)-1-[(S)-N-[(S)-1-carbonyl-3- phenylpropyl]alanyl]hexahydro-2-indolinecarboxylic acid (trandolaprilat) in isolated smooth muscle preparations.
1. Trandolaprilat was found to inhibit angiotensin I (Ang I)-induced contraction of the rat thoracic aorta, and to augment bradykinin(BK)-induced contraction of the guinea pig ileum. In inhibitory activity (IC50) on the Ang I induced contraction of the rat thoracic aorta, trandolaprilat was about 2.4 times as potent as enalaprilat. Concerning the augmenting activity (AC50) on bradykinin-induced contraction of the guinea pig ileum, the activity of trandolaprilat was similar to that of enalaprilat. 2. Trandolaprilat had no effect on contractions induced by norepinephrine, PGF2 alpha, 5-HT or CaCl2 in the thoracic aorta of rats. 3. Trandolaprilat produced endothelium-dependent relaxation. This relaxation was inhibited by NG-methyl-L-arginine treatment, suggesting that endothelium-dependent relaxation of trandolaprilat is related to endothelium-derived-relaxation-factor(EDRF/NO). Like trandolaprilat, captopril also produced endothelium-dependent relaxation, whereas enalaprilat had no effect.
Sekiguchi
N
N
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Ishii
Y
Y
Fujikura
H
H
Hasegawa
Y
Y
Takayanagi
I
I
D000803:Angiotensin I / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D015773:Enalaprilat / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D019323:omega-N-Methylarginine
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D019323:omega-N-Methylarginine; D000803:Angiotensin I; D001120:Arginine; D015773:Enalaprilat; C061095:trandolaprilat; D001920:Bradykinin