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. 1992 Jan;105(1):184–190. doi: 10.1111/j.1476-5381.1992.tb14233.x

Effects of inhibiting nitric oxide biosynthesis on the systemic and splanchnic circulation of rats with portal hypertension.

M P Pizcueta 1, J M Piqué 1, J Bosch 1, B J Whittle 1, S Moncada 1
PMCID: PMC1908593  PMID: 1596680

Abstract

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.

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Selected References

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