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 o f arterial vasodilation in cirrhosis. However, the subject is still co ntroversial. Aim: 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 rin gs was studied in vitro before and after nitric oxide blockade. Experi ments 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, i n comparison with the control group. This reduction in contractility t o phenylephrine was completely reversed by blocking NO synthesis. Conc lusion: The data presented indicate a dynamic decrease in contractile response to phenylephrine even at an early stage of secondary cirrhosi s. Reversibility of the affect after NO synthesis blockade suggests th at increased NO synthesis is a major factor in vascular hyporeactivity to vasoconstrictors in cirrhosis.