Enhanced contractility of the rat stomach during suppression of angiotensin converting enzyme by captopril in vitro.
1. 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. 2. Captopril, at concentrations greater than 0.3 microM, enhanced the spontaneous gastric motility (GM) in a concentration-dependent manner whereas concentrations less than 0.3 microM selectively potentiated 4 nM bradykinin (BK)-evoked gastric contractions without significantly affecting the spontaneous GM. 3. The kallikrein inhibitor, aprotinin (100 u ml-1), markedly antagonized the enhanced GM to 1.4 microM captopril and BK (4 nM)-evoked contractions, without affecting the contractions evoked by angiotensin 1 (10 nM) and acetylcholine (0.4 microM). The angiotensin II antagonist, saralasin (50 microM) failed to mimic aprotinin. 4. The enhanced GM to captopril was markedly inhibited by tetrodotoxin (1 microM), and partially inhibited by atropine (1 microM). 5. These results indicate that in vitro, captopril (greater than 0.3 microM) 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.
Rani
R
R
Department of Physiology, Banaras Hindu University, Varanasi, India.
Rao
K S
KS
D000109:Acetylcholine / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D007703:Peptidyl-Dipeptidase A / Q000502:physiology; D011312:Pressure; D051381:Rats; D012504:Saralasin / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects / Q000201:enzymology; D013779:Tetrodotoxin / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D013779:Tetrodotoxin; D001285:Atropine; D007611:Aprotinin; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D012504:Saralasin; D000109:Acetylcholine; D001920:Bradykinin