Endothelium-Dependent Potentiation of Prostaglandin F_2αInduced Contractions by (±)-[6]-Gingerol Is Inhibited by Cyclooxygenase- but Not Lipoxygenase-Inhibitors in Mouse Mesenteric Veins

Abstract

The mechanism of potentiation of prostaglandin (PG) F_2α-induced contraction of mouse mesenteric veins by (±)-[6]-gingerol was investigated in vitro. (±)-[6]-Gingerol (0.3 mM) potentiated the maximal contraction response elicited by PGF_2α (0.28 mM) in the presence of intact vascular endothelium, but not in its absence (de-endothelialized preparations). The potentiating effect was completely inhibited by cyclooxygenase inhibitors (0.2 mM aspirin and 0.2 mM indomethacin) and partly by calcium antagonists (2 μM verapamil, 8 nM nitrendipine and 1 μM ryanodine), but not inhibited by nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor and ONO-3708, a thromboxane (TX) A₂ antagonist. The potentiation by (±)-[6]-gingerol is also observed in mesenteric veins of streptozotocin-diabetic mice where the enhancement of PGF_2α-induced contraction is caused mainly by activation of lipoxygenase. The potentiaion of PGF_2α-induced contraction by (±)-[6]-gingerol may be caused by a cyclooxygenase-dependent release of vasoconstrictors, other than PGF_2α and TXA₂, or by inhibiting vasorelaxants released from endothelial cells of mouse mesenteric veins.