Nitric oxide attenuates endothelin-1-induced vasoconstriction in canine stomach.
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 {1,3-propanediamine-N-[4-1-(3-aminopropyl)-2-hydroxy-2-nitrosohydrazi no] butyl; a nitric oxide donor} 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.
Wood
J G
JG
Department of Surgery, University of Kansas Medical Center, Kansas City 66160, USA.
Zhang
Q
Q
Yan
Z Y
ZY
Cheung
L Y
LY
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004285:Dogs; D019332:Endothelin-1 / Q000494:pharmacology*; D007511:Ischemia / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009589:Nitrogen Oxides; D012016:Reference Values; D015424:Reperfusion; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology; D013270:Stomach / Q000098:blood supply*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000502:physiology*
D019332:Endothelin-1; D009589:Nitrogen Oxides; C091861:spermine nitric oxide complex; D013096:Spermine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester