Bradykinin-induced vasoconstriction and thromboxane release in perfused human placenta.

This investigation was performed to study the effects of bradykinin on the human fetoplacental circulation. The artery to a single placental cotyledon was perfused with RPMI medium (0.764 ml/min). Bradykinin caused a dose-related increase in vascular resistance. Because bradykinin is generally a vasodilator, we investigated the possibility that bradykinin-induced vasoconstriction was due to interactions with other pressor systems. Bradykinin and 9,11-dideoxy-9 alpha, 11 alpha-epoxymethanoprostaglandin F2 alpha (a stable thromboxane agonist) caused a dose-related increase in perfusion pressure. The bradykinin response was not mediated by angiotensin II, because bradykinin-induced vasoconstriction was not inhibited by saralasin, a competitive angiotensin antagonist. Bradykinin increased thromboxane B2 production by 62.0%. Prostaglandin E2 levels were increased by 86.7%, but prostaglandin E2 did not affect fetoplacental vascular resistance. Angiotensin II did not stimulate thromboxane B2 production and caused only a slight increase in prostaglandin E2. Indomethacin decreased the pressor response to angiotensin II. SQ29548, a specific thromboxane antagonist, caused a 61.6% inhibition of the bradykinin pressor response but did not change angiotensin II responsiveness. The data demonstrate that thromboxane is an important mediator of bradykinin-induced vasoconstriction in the isolated perfused human placenta.