Document Detail

Propranolol modulates the collateral vascular responsiveness to vasopressin via a G(α)-mediated pathway in portal hypertensive rats.
MedLine Citation:
PMID:  21736560     Owner:  NLM     Status:  MEDLINE    
Gastro-oesophageal variceal haemorrhage is one of the most dreadful complications of portal hypertension and can be controlled with vasoconstrictors. Nevertheless, sympathetic tone abnormality and vascular hyporesponsiveness in portal hypertension may impede the haemostatic effects of vasoconstrictors. Propranolol, a β-blocker binding the G-protein-coupled adrenoceptor, is a portal hypotensive agent. However, whether propranolol influences the collateral vasoresponse is unknown. Portal hypertension was induced by PVL (portal vein ligation) in Sprague-Dawley rats. In an acute study with an in situ perfusion model, the collateral responsiveness to AVP (arginine vasopressin) was evaluated with vehicle, propranolol (10 μmol/l), propranolol plus suramin (100 μmol/l, a G(α) inhibitor) or suramin pre-incubation. G(α) mRNA expression in the splenorenal shunt, the most prominent intra-abdominal collateral vessel, was measured. In the chronic study, rats received DW (distilled water) or propranolol (10 mg x kg(-1) of body weight x day(-1)) for 9 days. Then the concentration-response relationship of AVP and G(α) mRNA expression were assessed. Propranolol pre-incubation elevated the perfusion pressure changes of collaterals in response to AVP, which was inhibited by suramin. The splenorenal shunt G(αq) and G(α11) mRNA expression were enhanced by propranolol. The group treated with propranolol plus suramin had a down-regulation of G(α11) as compared with the propranolol group. Chronic propranolol treatment reduced mean arterial pressure, PP (portal pressure) and the perfusion pressure changes of collaterals to AVP. G(αs) expression was up-regulated. In conclusion, propranolol pre-incubation enhanced the portal-systemic collateral AVP responsiveness in portal hypertensive rats, which was related to G(αq) and G(α11) up-regulation. In contrast, the attenuated AVP responsiveness by chronic propranolol treatment was related to G(αs) up-regulation. The G(α) signalling pathway may be a therapeutic target to control variceal bleeding and PP in portal hypertension.
Jing-Yi Lee; Teh-Ia Huo; Hui-Chun Huang; Fa-Yauh Lee; Han-Chieh Lin; Chiao-Lin Chuang; Ching-Chih Chang; Sun-Sang Wang; Shou-Dong Lee
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical science (London, England : 1979)     Volume:  121     ISSN:  1470-8736     ISO Abbreviation:  Clin. Sci.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-08-22     Completed Date:  2011-10-17     Revised Date:  2011-10-20    
Medline Journal Info:
Nlm Unique ID:  7905731     Medline TA:  Clin Sci (Lond)     Country:  England    
Other Details:
Languages:  eng     Pagination:  545-54     Citation Subset:  IM    
Institute of Pharmacology, National Yang-Ming University, No. 155, Sect. 2, Li-Nong St., Taipei 11221, Taiwan.
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MeSH Terms
Adrenergic beta-Antagonists / administration & dosage,  pharmacology*
Antihypertensive Agents / pharmacology
Arginine Vasopressin / antagonists & inhibitors,  pharmacology*
Collateral Circulation / drug effects*
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Administration Schedule
Drug Interactions
GTP-Binding Protein alpha Subunits / antagonists & inhibitors,  genetics,  physiology
Gene Expression Regulation / drug effects
Hemodynamics / drug effects
Hypertension, Portal / physiopathology*
Liver Circulation / drug effects,  physiology
Propranolol / administration & dosage,  pharmacology*
Rats, Sprague-Dawley
Signal Transduction / drug effects
Suramin / pharmacology
Vasoconstrictor Agents / pharmacology*
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Antihypertensive Agents; 0/GTP-Binding Protein alpha Subunits; 0/Vasoconstrictor Agents; 113-79-1/Arginine Vasopressin; 145-63-1/Suramin; 525-66-6/Propranolol

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