Potentiative effect of angiotensin converting enzyme inhibitor on carrageenan edema in rats and the role of tissue kininogen.
Roles of kininogens in the development of potentiation of carrageenan edema in rats by angiotensin converting enzyme (ACE, = kininase II) inhibitor were studied. Carrageenan-induced edema was potentiated by oral administration of YS980, an ACE inhibitor, at a dose of 1 mg/kg 0.5 h before carrageenan injection. Intravenous injection of bromelain, a kininogen (KGN) depletor, at 3 mg/kg produced reduction of plasma KGN (total and high molecular weight KGN), which resulted in suppression of carrageenan edema and suppression of edema potentiation induced by YS980. Even after the plasma KGN level and inflammatory response to carrageenan returned to normal 24 h after the administration of bromelain, the potentiative effect of YS980 on the carrageenan edema remained suppressed. Thus, some factor other than plasma KGN is thought to be involved in the potentiation mechanisms on the carrageenan edema by YS980. Partially purified KGN from rat plasma (0.1 mg/site: liberated 4.4 X 10(-8) g bradykinin eq by trypsin digestion) completely restored the suppressed potentiation to normal by local preinjection to the inflamed site. In addition, such restoration was not observed in the animal in which plasma KGN was reduced 3 h after administration of bromelain. These results suggest that KGN, not only in plasma but also in tissue, play an active role in the development of potentiation of carrageenan edema by ACE inhibitor.
D015097:3-Mercaptopropionic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001963:Bromelains / Q000494:pharmacology; D002351:Carrageenan; D004487:Edema / Q000097:blood* / Q000209:etiology; D007704:Kininogens / Q000097:blood* / Q000302:isolation & purification; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D053778:Thiazolidines
D000806:Angiotensin-Converting Enzyme Inhibitors; D007704:Kininogens; D053778:Thiazolidines; C019135:(4R)-3-((2S)-3-mercapto-2-methylpropanoyl)-4- thiazolidinecarboxylic acid; D002351:Carrageenan; D001963:Bromelains; D015097:3-Mercaptopropionic Acid