Study of the mechanisms involved in the bradykinin-induced contraction of the pig iris sphincter muscle in vitro

Abstract

This study was designed to investigate the mechanisms by which bradykinin induces contraction of the pig iris sphincter muscle in vitro. Addition of bradykinin, Lys-bradykinin and Met-Lys-bradykinin to the pig iris sphincter resulted in a graded contraction with a mean EC 50s of 21, 11 and 5 nM, respectively. The bradykinin B 1 receptor agonist des-Arg 9-bradykinin only caused a slight contraction, measured 6 h after the tissue was set up. The B 2 receptor antagonists FR 173657 (( E)-3-(6-acetamido-3-pyridyl)- N [ N-2-4-dichloro-3-[(2-methyl-8-quinolinyl) oxymethyl] phenyl]- N-methylamino-carbonyl-ethyl] acrylamide) and Hoe 140 ( d-Arg 0-[Hyp 3, Thi 5, d-Tic 7, Oic 8]-bradykinin produced a graded shift to the right associated with marked inhibition of the bradykinin-induced contraction. Atropine, guanethidine or tetrodotoxin significantly reduced the bradykinin-induced contraction. Dazoxiben, an inhibitor of thromboxane A 2, and MK-571 (3-(3-(2-(7-chloro-2-quinolinyl) ethenyl) phenyl ((3-dimethyl amino-3oxo-propyl) thio) methyl) propanoic acid, a leukotriene D 4 receptor-selective antagonist, also caused inhibition of the bradykinin-mediated contraction. Cyclooxygenase-1 and -2 inhibitors, indomethacin, ibuprofen, valeryl salicylate and NS 398 ( N-[2-(cyclohexyloxy)-4-nitrophenyl]methanosulfonamide) all significantly inhibited the bradykinin-mediated contraction without affecting the carbachol-induced contraction of the pig iris sphincter. Taken together, these results indicate that the bradykinin-mediated contraction of the pig iris sphincter muscle seems to be mediated primarily by the activation of the B 2 receptor release of acetylcholine, noradrenaline and both cyclooxygenase-1 and -2 metabolites besides the release of leukotriene D 4 and tromboxane A 2 from the arachidonic acid pathway.