Effects of captopril and Icatibant on bradykinin (BK) and des [Arg9] BK in carrageenan-induced edema.
The effects of captopril, an angiotensin-converting enzyme inhibitor (ACEI), and a selective B2 kinin receptor antagonist (Icatibant) were examined on the paw edema and tissue contents of bradykinin (BK) and des[Arg9]BK following the intraplantar injection of carrageenan in rats. To this end, BK-like immunoreactivity (BK-LI) and des[Arg9]BK-LI were measured with highly sensitive and specific chemiluminescent enzyme immunoassays. Because pentobarbital significantly reduced the carrageenan-induced edema between 3 and 8 h, experiments were conducted in conscious rats. Icatibant (32.5 nmol/paw; intraplantar) significantly reduced carrageenan-induced paw edema between 3 and 8 h in captopril-untreated rats and at 1 and 3 h in captopril-treated rats (0.2 mg/kg x 5 days, per os). The paw content of BK-LI was increased 10-fold in captopril-untreated and 29-fold in captopril-treated rats 1 h after carrageenan injection. In parallel, des[Arg9]BK-LI was increased 8-fold in captopril-untreated and 24-fold in captopril-treated rats. Icatibant prevented the maximal increases in BK-LI and des[Arg9]BK-LI induced by carrageenan. It is concluded that inhibition of ACE by captopril enhanced the early production of endogenous BK and the edema formation induced by carrageenan through a B2 receptor-mediated mechanism. However, the B2 receptor does not appear to be involved in the late phase of the inflammatory response (from 5 to 24 h) to carrageenan in rats pretreated with ACEI. Although the concentrations of des[Arg9]BK were greater than those of BK, it is unlikely that B1 receptors play a significant role in this model of carrageenan-induced edema.
Département de Physiologie, Faculté de Médecine, Université de Montréal, Québec, Canada.
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D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000032:analysis* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002216:Captopril / Q000494:pharmacology*; D002351:Carrageenan / Q000494:pharmacology; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced*; D005534:Foot Diseases / Q000139:chemically induced*; D006614:Hindlimb / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018002:Receptors, Bradykinin / Q000145:classification; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D065168:Bradykinin Receptor Antagonists; D018002:Receptors, Bradykinin; C024626:bradykinin, des-Arg(9)-; C065679:icatibant; D002351:Carrageenan; D002216:Captopril; D001920:Bradykinin