Effects of inhibiting nitric oxide biosynthesis on the systemic and splanchnic circulation of rats with portal hypertension.
1. The effects of inhibiting endogenous nitric oxide (NO) synthesis with NG-monomethyl-L-arginine (L-NMMA) on the systemic and splanchnic circulation have been investigated in rats with experimental chronic portal hypertension, anaesthetized with ketamine. 2. Portal hypertension was induced by partial portal vein ligation, 2 weeks prior to study. This procedure induced a reduction in systemic arterial blood pressure (MAP), an increase in cardiac output as measured by radiolabelled microspheres, a reduction in peripheral and splanchnic vascular resistance and an increased portal venous inflow (PVI) and portal pressure, as compared to control non-ligated rats. 3. L-NMAA (6.25 and 50 mg kg-1, i.v.) dose-dependently increased MAP, reduced cardiac output and PVI, and increased peripheral and splanchnic vascular resistance. With L-NMMA (50 mg kg-1), PVI and the vascular resistances returned to values comparable to those determined in control non-ligated anaesthetized rats under resting conditions. 4. Porto-collateral resistance was also increased by these doses of L-NMMA, whereas portal pressure was unchanged. The increase in renal blood flow and decrease in renal vascular resistance also seen in portal-hypertensive rats was reversed by L-NMMA (50 mg kg-1). 5. These effects of L-NMMA (50 mg kg-1) were inhibited by prior administration of L-arginine (300 mg kg-1, i.v.). 6. These findings indicate that the chronic hyperdynamic circulatory characteristics following portal vein stenosis can be attenuated by L-NMMA. Thus, the excessive formation of endogenous NO may be implicated in the pathogenesis of the haemodynamic disturbances and splanchnic vasodilatation associated with chronic portal hypertension.
Pizcueta
M P
MP
Hepatic Haemodynamics Laboratory, Hospital Clinic i Provincial, University of Barcelona, Spain.
Piqué
J M
JM
Bosch
J
J
Whittle
B J
BJ
Moncada
S
S
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001775:Blood Circulation / Q000502:physiology*; D003250:Constriction; D006975:Hypertension, Portal / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013152:Splanchnic Circulation / Q000502:physiology*; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine