Aminoguanidine reverses aortic hyporeactivity to noradrenaline in portal vein-ligated rats.
To evaluate the role of the inducible and endothelial constitutive nitric oxide synthase in vascular hyporeactivity to vasopressors in portal hypertension, in vitro experiments were performed on intact and endothelium-denuded isolated thoracic aortic rings from portal vein-ligated and sham-operated rats in control conditions, in the presence of aminoguanidine alone, considered to be a selective inhibitor of the inducible nitric oxide synthase, and of aminoguanidine and the nonselective nitric oxide synthase inhibitor N(G)-nitro-L-arginine. In control conditions, hyporeactivity to noradrenaline was observed in both rings with and without endothelium from portal hypertensive versus sham-operated rats. In the rings with endothelium, aminoguanidine reverted this hyporeactivity in portal hypertensive rats. N(G)-Nitro-L-arginine caused an additional shift to the left of the concentration-response curves to noradrenaline in portal hypertensive and a similar shift in sham-operated rats. In the endothelium-denuded rings, aminoguanidine caused no significant changes in portal hypertensive rats, whereas a significant shift to the right in the sham-operated rats was noted, however similar as the shift in the time controls not preincubated with aminoguanidine. No significant further changes were observed after preincubation with the two inhibitors. The endothelium-dependent relaxations to acetylcholine were attenuated in portal hypertensive versus sham-operated rats; addition of aminoguanidine shifted the relaxation curves to the left in portal hypertensive but not in sham-operated rats. These results provide indirect evidence for an increased activity of the inducible nitric oxide synthase in the intact aortic rings but not in the endothelium-denuded rings from portal vein-ligated rats, where other factors seem to be responsible for the observed hyporeactivity to noradrenaline. The endothelial constitutive nitric oxide synthase in rings from portal vein-ligated rats shows a reduced activity which is alleviated after inhibition of the inducible enzyme by aminoguanidine.
Michielsen
P P
PP
Division of Gastroenterology, Faculty of Medicine, University of Antwerp (UIA), University Hospital of Antwerp, Belgium.
Boeckxstaens
G E
GE
Sys
S U
SU
Herman
A G
AG
Pelckmans
P A
PA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D006975:Hypertension, Portal / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D006146:Guanidines; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; C004479:pimagedine; D009638:Norepinephrine