Document Detail

Splanchnic hyposensitivity to glypressin in a haemorrhage/transfused rat model of portal hypertension: role of nitric oxide and bradykinin.
MedLine Citation:
PMID:  11099389     Owner:  NLM     Status:  MEDLINE    
Hyposensitivity to vasopressin is a well documented phenomenon in animals with portal hypertension and patients with cirrhosis subject to haemorrhage. Haemorrhage is associated with the endogenous release of bradykinin, which may subsequently stimulate the formation of nitric oxide (NO). The present study investigated the relative contribution of NO synthase (NOS) isoforms and the role of bradykinin in the pathogenesis of splanchnic hyposensitivity to a long-acting vasopressin analogue, glypressin, in rats with portal hypertension induced by partial portal vein ligation (PVL). At 14 days after the operation, systemic and portal haemodynamics were measured in stable or bleeding PVL rats receiving an intravenous infusion of glypressin (0.07 mg/kg). In the treatment groups, N(G)-nitro-L-arginine methyl ester (L-NAME; a non-selective NOS inhibitor), L-canavanine (a specific inhibitor of inducible NOS) or HOE 140 (a bradykinin B(2) receptor antagonist) was administered 45 min before the infusion of glypressin. In rats with a hypotensive haemorrhage, 4.5 ml of blood was withdrawn and 50% of the withdrawn blood was re-infused before the administration of glypressin or various inhibitors. Splanchnic hyposensitivity to glypressin was demonstrated in the haemorrhage/transfused PVL rats. The infusion of L-NAME elevated the mean arterial pressure in the bleeding PVL rats without the modulation of portal pressure. The addition of L-NAME or HOE 140, but not L-canavanine, significantly and similarly potentiated the portal-hypotensive effects of glypressin. It is concluded that constitutive NOS and bradykinin are responsible, at least partly, for the splanchnic hyposensitivity to glypressin observed in the early stages of the haemorrhage/transfused rat model of portal hypertension.
C J Chu; S L Wu; F Y Lee; S S Wang; F Y Chang; H C Lin; C C Chan; S D Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical science (London, England : 1979)     Volume:  99     ISSN:  0143-5221     ISO Abbreviation:  Clin. Sci.     Publication Date:  2000 Dec 
Date Detail:
Created Date:  2001-01-04     Completed Date:  2001-03-15     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7905731     Medline TA:  Clin Sci (Lond)     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  475-82     Citation Subset:  IM    
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No-201, Section 2, Shih-Pai Road, Taipei 11217, Taiwan.
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MeSH Terms
Blood Pressure / drug effects
Bradykinin / antagonists & inhibitors,  physiology*
Canavanine / pharmacology,  therapeutic use
Enzyme Inhibitors / pharmacology,  therapeutic use
Hypertension, Portal / drug therapy,  physiopathology*
NG-Nitroarginine Methyl Ester / pharmacology,  therapeutic use
Nitric Oxide / physiology*
Nitric Oxide Synthase / physiology
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Postoperative Hemorrhage / drug therapy,  physiopathology
Rats, Sprague-Dawley
Splanchnic Circulation / physiology*
Vasopressins / physiology*,  therapeutic use
Reg. No./Substance:
0/Enzyme Inhibitors; 10102-43-9/Nitric Oxide; 11000-17-2/Vasopressins; 50903-99-6/NG-Nitroarginine Methyl Ester; 543-38-4/Canavanine; 58-82-2/Bradykinin; EC Oxide Synthase; EC Oxide Synthase Type II; EC Oxide Synthase Type III; EC protein, rat; EC protein, rat

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