TY - JOUR
T1 - Vascular hyporesponsiveness in aortic rings from cirrhotic rats
T2 - Role of nitric oxide and endothelium
AU - Ortíz, M. Clara
AU - Fortepiani, Lourdes A.
AU - Martínez, Concha
AU - Atucha, Noemí M.
AU - García-Estañ, Joaquín
PY - 1996
Y1 - 1996
N2 - 1. The role of nitric oxide as mediator of the vascular alterations present in different models of experimental Liver cirrhosis is controversial. In the present study, we evaluated the role of nitric oxide and that of the endothelium in the response to phenylephrine and acetylcholine of isolated aortic rings from chronic bile duct-ligated (29 days) rats and their corresponding controls. Experiments were performed in rings with or without endothelium, in rings pretreated with N-ω-nitro-L-arginine methyl ester (10-4 mol/l) to inhibit nitric oxide synthesis and in rings pretreated with aminoguanidine (10-4 mol/l) to inhibit inducible nitric: oxide synthesis. 2. Under basal conditions, the maximum absolute tension developed in response to cumulative addition of phenylephrine was significantly decreased in rings from bile duct-ligated animals (1.62 ± 0.06g) compared with the control rings (2.15 ± 0.099). This hyporesponsiveness to phenylephrine of rings from bile duct-ligated animals was corrected after treatment with N-ω-nitro-L-arginine methyl ester and reduced, but not completely eliminated, in rings without endothelium. In contrast, aminoguanidine did not modify the lower response to phenylephrine rings from bile duct-ligated animals. ED(5o) values were not different between groups under any experimental conditions. 3. The endothelium-dependent vasodilatation to acetylcholine in phenylephrine-constricted rings was similar in both groups of animals, control and bile duct ligated, under all experimental conditions. N-ω-nitro-L-arginine methyl ester pretreatment and removal of the endothelium completely abolished the response to acetylcholine in cirrhotic and control rings. 4. These results demonstrate that in aortic rings from cirrhotic, bile duct-ligated rats, increased production of nitric oxide, mainly of endothelial origin, is responsible for the lower contractile response to phenylephrine. Our data, however, do not support the involvement of the inducible nitric oxide synthase isoform in this alteration. In contrast, endothelial vasodilatory response to acetylcholine is not altered in this model of cirrhosis, which indicates that not all mechanisms of nitric oxide release are abnormal.
AB - 1. The role of nitric oxide as mediator of the vascular alterations present in different models of experimental Liver cirrhosis is controversial. In the present study, we evaluated the role of nitric oxide and that of the endothelium in the response to phenylephrine and acetylcholine of isolated aortic rings from chronic bile duct-ligated (29 days) rats and their corresponding controls. Experiments were performed in rings with or without endothelium, in rings pretreated with N-ω-nitro-L-arginine methyl ester (10-4 mol/l) to inhibit nitric oxide synthesis and in rings pretreated with aminoguanidine (10-4 mol/l) to inhibit inducible nitric: oxide synthesis. 2. Under basal conditions, the maximum absolute tension developed in response to cumulative addition of phenylephrine was significantly decreased in rings from bile duct-ligated animals (1.62 ± 0.06g) compared with the control rings (2.15 ± 0.099). This hyporesponsiveness to phenylephrine of rings from bile duct-ligated animals was corrected after treatment with N-ω-nitro-L-arginine methyl ester and reduced, but not completely eliminated, in rings without endothelium. In contrast, aminoguanidine did not modify the lower response to phenylephrine rings from bile duct-ligated animals. ED(5o) values were not different between groups under any experimental conditions. 3. The endothelium-dependent vasodilatation to acetylcholine in phenylephrine-constricted rings was similar in both groups of animals, control and bile duct ligated, under all experimental conditions. N-ω-nitro-L-arginine methyl ester pretreatment and removal of the endothelium completely abolished the response to acetylcholine in cirrhotic and control rings. 4. These results demonstrate that in aortic rings from cirrhotic, bile duct-ligated rats, increased production of nitric oxide, mainly of endothelial origin, is responsible for the lower contractile response to phenylephrine. Our data, however, do not support the involvement of the inducible nitric oxide synthase isoform in this alteration. In contrast, endothelial vasodilatory response to acetylcholine is not altered in this model of cirrhosis, which indicates that not all mechanisms of nitric oxide release are abnormal.
KW - Acetylcholine
KW - Aorta
KW - Endothelium
KW - Liver cirrhosis
KW - Nitric oxide
KW - Phenylephrine
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U2 - 10.1042/cs0910733
DO - 10.1042/cs0910733
M3 - Article
C2 - 8976809
AN - SCOPUS:0029804856
VL - 91
SP - 733
EP - 738
JO - Clinical Science
JF - Clinical Science
SN - 0143-5221
IS - 6
ER -