Vascular kinin B1 and B2 receptor-mediated effects in the rat isolated perfused kidney-differential regulations

1 Bradykinin (BK) and analogs acting preferentially at kinin B-1 or B-2 receptors were tested on the rat isolated perfused kidney. Kidneys were perfused in an open circuit with Tyrode's solution. Kidneys preconstricted with prostaglandin F-2 alpha were used for the analysis of vasodilator responses. 2 BK induced a concentration-dependent renal relaxation (pD(2)=8.9+/-0.4); this vasodilator response was reproduced by a selective B-2 receptor agonist, Tyr(Me)(8)-BK (pD(2)=9.0+/-0.1) with a higher maximum effect (E-max=78.9+/-6.6 and 55.8+/-4.3% of ACh-induced relaxation respectively, n=6 and 19, P<0.02). Icatibant (10 nM), a selective B-2 receptor antagonist, abolished BK-elicited relaxation. Tachyphylaxis of kinin B-2 receptors appeared when repeatedly stimulated at 10 min intervals. 3 Des-Arg(9)-BK, a selective Bi receptor agonist, induced concentration-dependent vasoconstriction at micromolar concentration. Maximum response was enhanced in the presence of lisinopril(1 mu M) and inhibited by R 715 (8 mu M), a selective B-1 receptor antagonist. Des-Arg(9)-[Leu(8)]-BK behaved as an agonist. 4 A contractile response to des-Arg(9)-BK occurred after 1 h of perfusion and increased with time by a factor of about three over a 3 h perfusion. This post-isolation sensitization to des-Arg(9)-BK was abolished by dexamethasone (DEX, 30 mg kg(-1) i.p., 3 h before the start of the experiment and 10 mu M in perfusate) and actinomycin D (2 mu M). Acute exposure to DEX (10 mu M) had no effect on sensitized des-Arg(9)-BK response, in contrast to indomethacin (30 mu M) that abolished it. DEX pretreatment however had no effect on BK-induced renal vasodilation. 5 Present results indicate that the main renal vascular response to BK consists of relaxation linked to the activation of kinin B-2 receptors which rapidly desensitize. Renal B-1 receptors are also present and are time-dependently sensitized during the in vitro perfusion of the rat kidneys.