NITRIC-OXIDE ATTENUATES ENDOTHELIN-1-INDUCED VASOCONSTRICTION IN CANINE STOMACH

We previously observed that endothelin-1 (ET-1)-induced gastric vasoco nstriction 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 chlor alose-anesthetized dogs, we examined 1) responses to NG-nitro-L-argini ne methyl ester (L-NAME) alone and in combination with L-arginine, 2) whether L-NAME affects ET-1-induced vasoconstriction under normal cond itions and after ischemia-reperfusion, and 3) if spermine NONOate 3-am inopropyl)-2-hydroxy-2-nitrosohydrazino]butyl; a nitric oxide donor} a ttenuates the augmented response to ET-1 after ischemia-reperfusion. O ur results show that 1) L-NAME significantly increased baseline vascul ar resistance and this response was reduced by L-arginine, 2) ET-1-ind uced vasoconstriction was enhanced by L-NAME, and 3) administration of spermine NONOate during reperfusion largely attenuated the vasoconstr ictor response to ET-1 after ischemia-reperfusion. Our findings are co nsistent with the hypothesis that nitric oxide modulates responses to ET-1 under normal Conditions, and loss of this vasodilator after ische mia-reperfusion results in an augmented response to ET-1.