Endothelium-dependent potentiation of prostaglandin F2alpha-induced contractions by (+/-)-[6]-gingerol is inhibited by cyclooxygenase- but not lipoxygenase-inhibitors in mouse mesenteric veins

The mechanism of potentiation of prostaglandin (PG) F2alpha-induced contraction of mouse mesenteric veins by (+/-)-[6-gingerol was investigated in vitro. (+/-)-[6]-Gingerol (0.3mM) potentiated the maximal contraction response elicited by PGF2alpha (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 microM verapamil, 8 nM nitrendipine and 1 microM 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 PGF2alpha-induced contraction is caused mainly by activation of lipoxygenase. The potentiation of PGF2alpha-induced contraction by (+/-)-[6]-gingerol may be caused by a cyclooxygenase-dependent release of vasoconstrictors, other than PGF2alpha and TXA2, or by inhibiting vasorelaxants released from endothelial cells of mouse mesenteric veins.