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.
Hata
Y
Y
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Sugitani, Japan.
Pancho
L R
LR
Nojima
H
H
Kimura
I
I
D000818:Animals; D002396:Catechols; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D015237:Dinoprost / Q000494:pharmacology*; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000502:physiology*; D005233:Fatty Alcohols / Q000494:pharmacology*; D008084:Lipoxygenase / Q000502:physiology; D008297:Male; D008642:Mesenteric Veins / Q000187:drug effects / Q000502:physiology; D051379:Mice; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D013311:Streptozocin; D014661:Vasoconstriction / Q000187:drug effects*
D002396:Catechols; D005233:Fatty Alcohols; D013311:Streptozocin; C007845:gingerol; D015237:Dinoprost; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases