We previously observed that endothelin-1 (ET-1)-induced gastric vasoconstriction is enhanced after ischemia-reperfusion. The purpose of our present study was to examine the role of nitric oxide in regulating ET-1-induced vasoconstriction under normal conditions and after ischemia-reperfusion. Using a mechanically perfused stomach segment from chloralose-anesthetized dogs, we examined 1) responses to NG-nitro-L-arginine methyl ester (L-NAME) alone and in combination with L-arginine, 2) whether L-NAME affects ET-1-induced vasoconstriction under normal conditions and after ischemia-reperfusion, and 3) if spermine NONOate inverted question mark1,3-propanediamine-N-[4-1-(3-aminopropyl)-2-hydroxy-2-nitrosohydrazi no] butyl; a nitric oxide donor inverted question mark attenuates the augmented response to ET-1 after ischemia-reperfusion. Our results show that 1) L-NAME significantly increased baseline vascular resistance and this response was reduced by L-arginine, 2) ET-1-induced vasoconstriction was enhanced by L-NAME, and 3) administration of spermine NONOate during reperfusion largely attenuated the vasoconstrictor response to ET-1 after ischemia-reperfusion. Our findings are consistent with the hypothesis that nitric oxide modulates responses to ET-1 under normal conditions, and loss of this vasodilator after ischemia-reperfusion results in an augmented response to ET-1.
FK409, a novel nitric oxide donor, inhibits endothelin-1 production in cultured endothelial cells