Role of nitric oxide in hyporeactivity to noradrenaline of isolated aortic rings in portal hypertensive rats.
To test the hypothesis that induction of nitric oxide synthase causes systemic vascular hyporesponsiveness to vasopressors in portal hypertension, we performed in vitro experiments on isolated thoracic aortic rings from partial portal vein ligated or sham operated rats at 3 weeks postoperatively. The concentration-response curves to noradrenaline of intact and endothelium-denuded aortic rings from portal hypertensive rats were significantly shifted to the right as compared to those from sham operated animals. Maximal contractions did not significantly differ. Addition of NG-nitro-L-arginine, a specific inhibitor of nitric oxide synthase, shifted the curves to the left in both sham operated and portal hypertensive rats, so that in intact rings, the concentrations of noradrenaline producing half-maximal response did not significantly differ any more between sham operated and portal vein ligated rats. In endothelium-denuded rings, a hyporeactivity to noradrenaline persisted in portal vein ligated rats. Furthermore, NG-nitro-L-arginine induced an additional significant increase in the maximal response to noradrenaline in sham operated as compared to portal hypertensive rats. The endothelium-dependent relaxations to acetylcholine were attenuated in portal hypertensive rats as compared to sham operated animals. From these results, it can be concluded that increased nitric oxide production in the vascular wall of thoracic aorta of portal hypertensive rats is involved in their hyporesponsiveness to noradrenaline. Our findings in endothelium-denuded rings indicate the involvement of the inducible nitric oxide synthase in the smooth muscle layer. Involvement of an inducible nitric oxide synthase in the endothelium cannot be excluded. The endothelial constitutive nitric oxide synthase, however, seems to be suppressed in portal vein ligated rats.
Michielsen
P P
PP
Division of Gastroenterology, Faculty of Medicine, University of Antwerp (UIA), Antwerpen-Wilrijk, Belgium.
Boeckxstaens
G E
GE
Sys
S U
SU
Herman
A G
AG
Pelckmans
P A
PA
D000109:Acetylcholine / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology; D006975:Hypertension, Portal / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine