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.
View full abstract