Different prostanoids are involved in bradykinin-induced endothelium-dependent and -independent vasoconstriction in rat mesenteric resistance arteries.

Mechanisms underlying bradykinin-induced vasoconstriction were investigated in rat perfused mesenteric vascular beds with active tone. In preparations with intact endothelium, bolus injections of bradykinin (1 to 1,000 pmol) dose-dependently produced three-phase vascular effects, which consisted of a first-phase vasodilation followed by a second-phase vasoconstriction and a subsequent third-phase vasodilation; these effects were abolished by FR172357 (bradykinin B(2)-receptor antagonist), but not by des-Arg(9)-[Leu(8)]-bradykinin (bradykinin B(1)-receptor antagonist). In preparations with intact endothelium, indomethacin (cyclooxygenase inhibitor), seratrodast (thromboxane A(2) (TXA(2))-receptor antagonist), ONO-3708 (TXA(2)/prostaglandin H(2) (PGH(2))-receptor antagonist) or ozagrel (TXA(2) synthesis inhibitor) markedly inhibited the bradykinin-induced vasoconstriction. In preparations without endothelium, the bradykinin-induced vasoconstriction was abolished by indomethacin and ONO-3708, while seratrodast and ozagrel had no effect. These results suggest that the endothelium-dependent vasoconstriction of bradykinin is mainly mediated by TXA(2) and that prostanoids other than TXA(2), probably PGH(2), in mesenteric vascular smooth muscle are responsible for bradykinin-induced endothelium-independent vasoconstriction.