The role of nitric oxide in the vascular hyporesponsiveness to methoxamine in portal hypertensive rats

✍ Scribed by Fa-Yauh Lee; Agustin Albillos; Luis A. Colombato; Roberto J. Groszmann

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 607 KB
• Volume: 16
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840160430

✦ Synopsis

This study examined whether an increased activity of the endothelium-derived relaxing factor, nitric oxide, may account for the hyporesponsiveness to vasoconstrictors in portal hypertension. W e performed dose-response curves to methoxamine, an eadrenoceptor agonist, with and without N"dtr0-Larginine, a spec%c inhibitor of nitric oxide synthesis, in experimental portal hypertension. Partial portal vein-ligated or sham-operated rats were pretreated with a continuous intravenous infusion of either Nunitro-L-arginine (50 pg-kg-' .min-') or saline. Thirty minutes after starting the infusion of N--nitro-~arglnine or saline an infusion of methoxamine (10,30 and 100 Fg-kg-l. min-l) was added. Total peripheral resistance was calculated from mean arterial preeeure and cardiac index. Repeated measurements of cardiac index were performed by a thermodilution technique. In portal vein-ligated rats pretreated with saline, the increase in total peripheral resistance after methoxamine infusion was significantly less than that of sham-operated rats (0.2 f 0.1 vs. 1.0 2 0.3,0.6 f 0.1 vs. min -100 gm, p < 0.06, methoxamine 10, 30 and 100 Fg-kg-'min-l, respectively). In the presence of N"nitro-L-arginine, the change in total peripheral resistance after methoxamine infusion was similar in both groups (p > 0.05). In conclusion, this study demonstrates that a vascular hyporesponsiveness to methoxamine is present in portal vein-ligated rats and that this hyporesponsiveness is reversed by blockade of nitric oxide. This suggests that nitric oxide playa an important role in the arterial vasodilation obtmrved in portal hypertensive states. (HEPATOLOGY 1992;16 1043-1048.)

1.6 * 0.3 and 3.7 f 0.5 VS. 6.1 f 0.7 111111 Hg-ml-'.

Portal hypertension is characterized by pronounced arterial vasodilation and increased systemic and regional organ blood flow. This vasodilation leads to