In vitro and in vivo effects of kinin B(1) and B(2) receptor agonists and antagonists in inbred control and cardiomyopathic hamsters.
The aims of this study were to examine the possible alterations occurring in the effects of kinins on isolated aortae of inbred control (CHF 148) and cardiomyopathic (CHF 146) hamsters of 150 - 175 and 350 - 375 days of age. Bradykinin (BK) and desArg(9)BK contracted isolated aortae (with or without endothelium) of hamsters of both strains and ages. After tissue equilibration (90 min), responses elicited by both kinin agonists were stable over the time of experiments. The patterns of isometric contractions of BK and desArg(9)BK were however found to be different; desArg(9)BK had a slower onset and a longer duration of action than BK. Potencies (pEC(50) values) of BK in all groups of hamsters were significantly increased by preincubating the tissues with captopril (10(-5) M). No differences in the pEC(50) values and the E(max) values for BK or desArg(9)BK were seen between isolated vessels from inbred control and cardiomyopathic hamsters. The myotropic effect of BK was inhibited by the selective non peptide antagonist, FR 173657 (pIC(50) 7.25+/-0.12 at the bradykinin B(2) receptor subtype (B(2) receptor)). Those of desArg(9)BK, at the bradykinin B(1) receptor subtype (B(1) receptor) were abolished by either R 715 (pIC(50) of 7. 55+/-0.05; alpha(E) = 0), Lys[Leu(8)]desArg(9)BK (pIC(50) of 7.21+/-0. 01; alpha(E) = 0.22) or [Leu(8)]desArg(9)BK (pIC(50) of 7.25+/-0.02; alpha(E) = 0.18). FR 173657 had no agonistic activity, exerted a non competitive type of antagonism and was poorly reversible (lasting more than 5 h) from B(2) receptor. In vivo, FR 173657 (given per os at 1 and 5 mg kg(-1), 1 h before the experiment) antagonized the acute hypotensive effect of BK in anaesthetized hamsters. It is concluded that aging and/or the presence of a congenital cardiovascular disorder in hamsters are not associated with changes in the in vitro aortic responses to either BK or desArg(9)BK.
Hallé
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S
Department of Pharmacology, Medical School, Université de Sherbrooke, 3001 12th North Avenue, Sherbrooke, Québec J1H 5N4, Canada. stepaniehalle@hotmail.com
Gobeil
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Ouellette
J
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Lambert
C
C
Regoli
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D
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D065168:Bradykinin Receptor Antagonists; D009202:Cardiomyopathies / Q000378:metabolism* / Q000503:physiopathology; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D008297:Male; D008647:Mesocricetus; D011804:Quinolines / Q000494:pharmacology*; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000819:agonists / Q000378:metabolism*; D014661:Vasoconstriction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D065168:Bradykinin Receptor Antagonists; C105311:FR 173657; D011804:Quinolines; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin