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

Abstract

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. We performed dose-response curves to methoxamine, an alpha-adrenoceptor agonist, with and without N omega-nitro-L-arginine, a specific 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 N omega-nitro-L-arginine (50 micrograms.kg-1.min-1) or saline. Thirty minutes after starting the infusion of N omega-nitro-L-arginine or saline an infusion of methoxamine (10, 30 and 100 micrograms.kg-1.min-1) was added. Total peripheral resistance was calculated from mean arterial pressure 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 +/- 0.1 vs. 1.0 +/- 0.3, 0.6 +/- 0.1 vs. 1.6 +/- 0.3 and 3.7 +/- 0.5 vs. 6.1 +/- 0.7 mm Hg.ml-1.min.100 gm, p less than 0.05, methoxamine 10, 30 and 100 micrograms.kg-1.min-1, respectively). In the presence of N omega-nitro-L-arginine, the change in total peripheral resistance after methoxamine infusion was similar in both groups (p greater than 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.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: F Y Lee, A Albillos, L A Colombato, R J Groszmann
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 16 Issue 4 Pg. 1043-8 (Oct 1992) ISSN: 0270-9139 [Print] United States
• PMID: 1398484 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Nitroarginine
• Nitric Oxide
• Arginine
• Methoxamine

Topics

• Animals
• Arginine (analogs & derivatives, pharmacology)
• Blood Pressure (drug effects)
• Blood Vessels (drug effects)
• Dose-Response Relationship, Drug
• Hypertension, Portal (physiopathology)
• Male
• Methoxamine (pharmacology)
• Nitric Oxide (metabolism)
• Nitroarginine
• Rats
• Rats, Sprague-Dawley
• Vascular Resistance (drug effects)