Time course-dependent evolution of nitric oxide-mediated arterial hyporeactivity to phenylephrine in rats with ligated bile duct.
BACKGROUND
Nitric oxide (NO) may be heavily involved the phenomenon of arterial vasodilation in cirrhosis. However, the subject is still controversial.


OBJECTIVE
This study therefore characterizes the dynamic role of the NO system during development of experimental cirrhosis.


METHODS
The contractile response to phenylephrine of thoracic rat aortic rings was studied in vitro before and after nitric oxide blockade. Experiments were performed 1, 2, 3, and 4 weeks after induction of cirrhosis via bile duct ligation with an appropriate control group.


RESULTS
In bile duct-ligated rats reduction of the maximum contractile response to phenylephrine was 4.4 +/- 7.3% after 1 week, 22.7 +/- 8.7% after 2 weeks, 48.4 +/- 8.3% after 3 weeks, and 64.6 +/- 8.9% after 4 weeks, in comparison with the control group. This reduction in contractility to phenylephrine was completely reversed by blocking NO synthesis.


CONCLUSIONS
The data presented indicate a dynamic decrease in contractile response to phenylephrine even at an early stage of secondary cirrhosis. Reversibility of the effect after NO synthesis blockade suggests that increased NO synthesis is a major factor in vascular hyporeactivity to vasoconstrictors in cirrhosis.
Kimpel
M
M
Dept. of Surgery, Faculty of Medicine, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
Folz
I C
IC
Hanisch
E
E
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology*; D001652:Bile Ducts; D066298:In Vitro Techniques; D008026:Ligation; D008105:Liver Cirrhosis, Biliary / Q000503:physiopathology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D009569:Nitric Oxide