Converting enzyme inhibition in the rat by captopril is accompanied by potentiation of carrageenin-induced inflammation.
Hind paw oedema in rats, measured by plethysmography or extravasation of Evans Blue dye into the skin, after subplantar injection of submaximal doses of carrageenin (1-100 micrograms) was significantly increased for 4 h during kininase II inhibition with captopril (1 mg kg-1, s.c.). Submaximal oedema, as assessed by paw swelling, after subplantar bradykinin (0.1-1.0 microgram) was also significantly increased after subcutaneous administration of this dose of captopril, whereas that in response to either histamine (2-20 micrograms) or prostaglandin E2 (2 micrograms) was unchanged. The pain threshold of the paw, injected with carrageenin (1 microgram) was lowered significantly after subcutaneous administration of captopril (1 mg kg-1). Potentiation by captopril (1 mg kg-1, s.c.) of paw swelling in response to intraplantar carrageenin (100 micrograms) or bradykinin (1 microgram) was reduced by prior subcutaneous administration of indomethacin (5 mg kg-1). It is suggested that normally, tissue kininase II activity is sufficient to decrease the inflammatory response of the hind paw to carrageenin or bradykinin. After inhibition of kininase II with captopril, bradykinin levels are increased and interact with concomitantly released prostaglandins to potentiate inflammation.
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D002351:Carrageenan; D015232:Dinoprostone; D004357:Drug Synergism; D004487:Edema / Q000139:chemically induced; D007249:Inflammation / Q000139:chemically induced*; D008297:Male; D010146:Pain / Q000139:chemically induced; D011392:Proline / Q000031:analogs & derivatives*; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D011458:Prostaglandins E; D002351:Carrageenan; D011392:Proline; D002216:Captopril; D015232:Dinoprostone; D001920:Bradykinin