The role of increased nitric oxide in the vascular hyporeactivity to noradrenaline in long-term portal vein ligated rats.
To test the possible role of nitric oxide production in long-term portal vein ligation in the rat, where the hyperdynamic circulation was reported to be absent, in vivo experiments on isolated thoracic aortic rings from partial portal vein ligated or sham-operated rats were performed, 6 months postoperatively. The concentration-response curves to noradrenaline of both intact and endothelium-denuded rings from portal hypertensive rats were significantly shifted to the right as compared to those from sham-operated animals. In intact rings, addition of NG-nitro-L-arginine, a specific inhibitor of nitric oxide synthase, resulted in a significant shift of the curves to the left in sham-operated and portal vein ligated rats. In endothelium-denuded rings, addition of NG-nitro-L-arginine resulted in a significant shift of the curves to the left in portal vein ligated but not in sham-operated animals. After blockade of the nitric oxide biosynthesis with NG-nitro-L-arginine, the negative logarithm of the concentration of nonadrenaline causing half-maximal response did not significantly differ any more between portal vein ligated and sham-operated rats; in endothelium-denuded rings hyporeactivity to noradrenaline persisted in portal vein ligated rats. Only in the intact rings did NG-nitro-L-arginine significantly increase the maximal contractions. No differences were demonstrated in endothelium-dependent relaxations to acetylcholine between sham-operated and portal hypertensive animals. From these results, it can be concluded that in vitro aortic hyporeactivity to noradrenaline is still present in long-term portal vein ligated rats, and that it results at least partially from activation of the L-arginine: nitric oxide pathway in the aortic vascular wall.
Michielsen
P P
PP
Division of Gastroenterology, Faculty of Medicine, University of Antwerp (UIA), Belgium.
Boeckxstaens
G E
GE
Sys
S U
SU
Herman
A G
AG
Pelckmans
P A
PA
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006975:Hypertension, Portal / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D009638:Norepinephrine