Document Detail

Haemodynamic and hormonal responses to long-term inhibition of nitric oxide synthesis in rats with portal hypertension.
MedLine Citation:
PMID:  8891579     Owner:  NLM     Status:  MEDLINE    
In portal hypertension, the role of the vasorelaxant nitric oxide (NO) in long-term splanchnic and systemic vascular tone regulation is unclear. This study examined the effects of long-term administration of a NO synthesis inhibitor on haemodynamics in portal hypertensive rats. Rats were randomly assigned to receive either water (placebo) or 100 mg/ of oral N-nitro-L-arginine methylester (L-NAME) for 28 days. At 14 days, the portal vein was ligated in 10 rats from each group. At 28 days, splanchnic and systemic blood flows were measured in 20 normal and 20 portal vein stenosed rats. Plasma atrial natriuretic peptide (ANP) concentrations as well as plasma and urinary cyclic guanosine monophosphate (cGMP) levels were also measured. Porto-systemic shunts were measured in other portal vein stenosed animals that had or had not received L-NAME. Portal vein stenosed rats that received L-NAME had significantly lower portal tributary blood flow and percentages of portal-systemic shunting (7.3 +/- 0.5 versus 3.7 +/- 0.2 ml/min.100 g and 96 +/- 1 versus 68 +/- 5%, respectively) and higher hepatocollateral vascular resistance (147 +/- 10 versus 295 +/- 30 g.10(3), respectively) than placebo portal vein stenosed rats. Portal pressure, ANP and cGMP levels did not differ between the groups. Arterial pressure was significantly higher and cardiac index lower after L-NAME than after placebo. Normal rats had similar but less marked L-NAME-induced responses than portal hypertensive rats. The presence of a long-term L-NAME-induced vasoconstriction in collateral vessels and splanchnic and systemic arterioles in portal vein stenosed rats indicates that a NO-mediated vasodilator tone may contribute to the development and the maintenance of collateral circulation as well as splanchnic and systemic vasodilation in portal hypertension. Moreover, the NO-mediated vasodilator tone in portal hypertensive animals seems to be increased.
C Pilette; R Moreau; P Sogni; P Kirstetter; S Cailmail; E Pussard; D Lebrec
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  European journal of pharmacology     Volume:  312     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1996 Sep 
Date Detail:
Created Date:  1997-02-06     Completed Date:  1997-02-06     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  63-8     Citation Subset:  IM    
Laboratoire d'Hémodynamique Splanchnique, Hôpital Beaujon, Clichy, France.
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MeSH Terms
Atrial Natriuretic Factor / blood
Cyclic GMP / blood
Enzyme Inhibitors / pharmacology*
Hemodynamics / drug effects*
Hypertension, Portal / physiopathology*
NG-Nitroarginine Methyl Ester / pharmacology*
Nitric Oxide Synthase / antagonists & inhibitors*
Rats, Sprague-Dawley
Vasoconstriction / drug effects
Reg. No./Substance:
0/Enzyme Inhibitors; 50903-99-6/NG-Nitroarginine Methyl Ester; 7665-99-8/Cyclic GMP; 85637-73-6/Atrial Natriuretic Factor; EC Oxide Synthase

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