Conversion of B1 kinin receptor-mediated vascular relaxation to contraction.

We have previously reported that des-Arg9-bradykinin can relax the phenylephrine-precontracted rabbit mesenteric artery through B1 kinin receptor stimulation and the subsequent release of prostaglandins. In the present study, we have found that this relaxant response can be converted to a contractile response by the cyclooxygenase inhibitor indomethacin. Contraction was dose-dependent and was blocked by the B1 receptor antagonist [Leu8]des-Arg9-bradykinin, with a pA2 value obtained by Schild regression similar to that reported for relaxation in the absence of indomethacin. Des-Arg10-kallidin (ED50 = 5.0 +/- 0.9 X 10(-9) M) was 16 times more potent than des-Arg9-bradykinin (ED50 = 8.1 +/- 0.8 X 10(-8) M) in contracting the indomethacin-treated artery and was also blocked by [Leu8]des-Arg9-bradykinin. In contrast, only 13 out of 24 indomethacin-treated vessels contracted in response to bradykinin, which had only one tenth and one 160th the potency (ED50 = 9.9 +/- 1.8 X 10(-7) M) of des-Arg9-bradykinin and des-Arg10-kallidin, respectively. B1 kinin receptor-mediated contraction in the presence of indomethacin was unaffected by the dual cyclooxygenase-lipoxygenase inhibitor BW 755c. These results indicate that des-Arg-kinins can stimulate both relaxation and contraction of the phenylephrine-precontracted rabbit mesenteric artery through stimulation of B1 kinin receptors. The relaxation is dependent on the release of prostaglandins, while the contraction may represent a direct effect.