The role of nitric oxide in the vascular hyporesponsiveness to methoxamine in portal hypertensive rats.
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)
Lee
F Y
FY
Hepatic Hemodynamic Laboratory, Veterans Affairs Medical Center, West Haven, Connecticut 06516.
Albillos
A
A
Colombato
L A
LA
Groszmann
R J
RJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006975:Hypertension, Portal / Q000503:physiopathology*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects
D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D008729:Methoxamine