Conversion of B1 Kinin Receptor-Mediated Vascular Relaxation to Contraction

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 1987-06, Vol.9 (6, Part 2 Suppl III), p.III-1-III-5
• Main Authors: CHURCHILL, LAURIE, WARD, PATRICK E
• Format: Article
• Language: English
• Subjects: 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; Animals; Applied sciences; Bradykinin - analogs & derivatives; Bradykinin - pharmacology; Dose-Response Relationship, Drug; Exact sciences and technology; Indomethacin - pharmacology; Kallidin - analogs & derivatives; Kallidin - pharmacology; Male; Other techniques and industries; Pyrazoles - pharmacology; Rabbits; Receptors, Bradykinin; Receptors, Neurotransmitter - physiology; Vasoconstriction - drug effects; Vasodilation - drug effects
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.hyp.9.6_pt_2.iii1

We have previously reported that des-Arg-bradykinin can relax the phenylephrineprecontracted rabbit mesenteric artery through B, 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 B, 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-Argl0-kallidin (ED50 = 5.0 ± 0.9 × 10 M) was 16 times more potent than des-Arg-bradykinin (ED50 = 8.1 ± 0.8 × 1(H 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 (EDS0 = 9.9± 1.8 × 10–7 M) of des-Arg-bradykinin and des-Argl0-kallidin, respectively. B, kinin receptor-mediated contraction in the presence of indomethacin was unaffected by the dual cyclooxygenase-Iipoxygenase inhibitor BW 755c. These results indicate that des-Arg-kinins can stimulate both relaxation and contraction of the phenylephririe-precontracted rabbit mesenteric artery through stimulation of B, kinin receptors. The relaxation is dependent on the release of prostaglandins, while the contraction may represent a direct effect.