N omega-nitro-L-arginine administration corrects peripheral vasodilation and systemic capillary hypotension and ameliorates plasma volume expansion and sodium retention in portal hypertensive rats.
In portal hypertensive states, peripheral vasodilation leads to sodium retention and plasma volume expansion. N omega-nitro-L-arginine, a specific biosynthesis inhibitor of the vasodilator nitric oxide, has been shown to acutely reverse peripheral vasodilation and the vascular hyporesponsiveness to endogenous and exogenous vasoconstrictors observed in portal hypertensive rats. This study investigated whether N omega-nitro-L-arginine treatment in portal hypertensive rats prevents peripheral vasodilation and therefore ameliorates plasma volume expansion and sodium retention. For 2 days before partial portal vein ligation or sham operation and then continuously for 4 days after the operation, animals received either placebo (0.9% saline) or N omega-nitro-L-arginine (approximately 2 micrograms/kg/min) intravenously through a subcutaneously implanted Alzet osmotic pump (model 2ML1; Alza, Palo Alto, CA). In portal hypertensive rats, N omega-nitro-L-arginine treatment significantly increased mean arterial pressure (placebo vs. N omega-nitro-L-arginine, 123 +/- 4 vs. 150 +/- 2 mm Hg, respectively; p < 0.001) and systemic vascular resistance (3.8 +/- 0.2 vs. 5.6 +/- 0.3 mm Hg/ml/min/100 gm body weight; p < 0.001), associated with a decrease in the cardiac index (33.5 +/- 1.0 vs. 27.0 +/- 1.1 ml/min/100 gm body weight; p < 0.001). N omega-nitro-L-arginine treatment also induced a decrease in plasma volume (4.6 +/- 0.1 vs. 4.1 +/- 0.1 ml/100 gm body weight; p < 0.001) and extracellular sodium space (39.4 +/- 0.7 vs. 37.4 +/- 0.4 ml/100 gm body weight; p < 0.05) without changes in serum sodium.(ABSTRACT TRUNCATED AT 250 WORDS)
Lee
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Hepatic Hemodynamic Laboratory, Veterans Affairs Medical Center, West Haven, Connecticut 06516.
Colombato
L A
LA
Albillos
A
A
Groszmann
R J
RJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D001810:Blood Volume / Q000187:drug effects*; D002196:Capillaries / Q000187:drug effects; D005110:Extracellular Space / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006975:Hypertension, Portal / Q000503:physiopathology*; D008297:Male; D019335:Nitroarginine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects*
D019335:Nitroarginine; D001120:Arginine; D012964:Sodium