sq-29548 and imidazole

1. Administration of bradykinin caused dose-dependent vasoconstriction in rat isolated perfused mesenteric arteries precontracted with noradrenaline. 2. The vasoconstrictor response was not mediated by BK1-bradykinin receptors. 3. Inhibition of cyclo-oxygenase with indomethacin, aspirin or meclofenamate abolished the vasoconstrictor effect of bradykinin, showing that a member of the arachidonic acid cascade may be involved. 4. Inhibitors of thromboxane synthesis (imidazole and UK 38485) did not affect or only reduced the bradykinin-induced vasoconstriction. 5. The endoperoxide H2/thromboxane A2 receptor antagonist SQ 29548 significantly reduced the vasoconstrictor effect of bradykinin, but did not affect the vasoconstrictor response to noradrenaline, adrenaline, vasopressin, 5-hydroxytryptamine or prostaglandins. 6. The eicosanoid(s) that mediate bradykinin-induced vasoconstriction appear to be synthesized outside the arterial endothelium. 7. The data suggest that the vasoconstrictor effect of bradykinin in the rat isolated mesenteric artery is mediated by vasoconstrictor arachidonic acid metabolites including the cyclic endoperoxides and/or the thromboxanes.

Topics: Animals; Aspirin; Bradykinin; Bridged Bicyclo Compounds, Heterocyclic; Cyclooxygenase Inhibitors; Eicosanoids; Endothelium, Vascular; Fatty Acids, Unsaturated; Hydrazines; Imidazoles; In Vitro Techniques; Indomethacin; Meclofenamic Acid; Mesenteric Arteries; Norepinephrine; Rats; Receptors, Prostaglandin; Receptors, Thromboxane; Thromboxane A2; Thromboxane-A Synthase; Vasoconstriction