In vitro and in vivo effects of kinin B-1 and B-2 receptor agonists and antagonists in inbred control and cardiomyopathic hamsters

1 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) an d cardiomyopathic (CHF 146) hamsters of 150-175 and 350-375 days of age. 2 Bradykinin (BK) and destArg(9)BK contracted isolated aortae (with or with out endothelium) of hamsters of both strains and ages. After tissue equilib ration (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 on set and a longer duration of action than BK. 3 Potencies (pEC(50) values) of BK in all groups of hamsters were significa ntly increased by preincubating the tissues with captopril (10(-5) M). 4 No differences in the pEC(50) values and the E-max values for BK or desAr g(9)BK were seen between isolated vessels from inbred control and cardiomyo pathic hamsters. 5 The myotropic effect of BK was inhibited by the selective non peptide ant agonist, FR 173657 (PIC50 7.25 +/- 0.12 at the bradykinin B-2 receptor subt ype (B-2 receptor)). Those of desArg(9)BK, at the bradykinin B-1 receptor s ubtype (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). 6 FR 173657 had no agonistic activity, exerted a non competitive type of an tagonism and was poorly reversible (lasting more than 5 h) from B-2 recepto r. III vivo, FR 173657 (given per os at 1 and 5 mg kg(-1), 1 h before the e xperiment) antagonized the acute hypotensive effect of BE; in anaesthetized hamsters. 7 It is concluded that aging and/or the presence of a congenital cardiovasc ular disorder in hamsters an not associated with changes in the in vitro ao rtic responses to either BK or desArg(9)BK.