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.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000494:pharmacology; D007609:Kallidin / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology; D011817:Rabbits; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D011720:Pyrazoles; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; C024626:bradykinin, des-Arg(9)-; D007609:Kallidin; C051090:bradykinin, Leu(8)-des-Arg(9)-; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; C052787:kallidin, des-Arg(10)-; D001920:Bradykinin; D007213:Indomethacin