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 Gα inhibitor) or suramin pre-incubation. Gα 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·kg−1 of body weight·day−1) for 9 days. Then the concentration–response relationship of AVP and Gα 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 Gαq and Gα11 mRNA expression were enhanced by propranolol. The group treated with propranolol plus suramin had a down-regulation of Gα11 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. Gαs expression was up-regulated. In conclusion, propranolol pre-incubation enhanced the portal-systemic collateral AVP responsiveness in portal hypertensive rats, which was related to Gαq and Gα11 up-regulation. In contrast, the attenuated AVP responsiveness by chronic propranolol treatment was related to Gαs up-regulation. The Gα signalling pathway may be a therapeutic target to control variceal bleeding and PP in portal hypertension.
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August 22 2011
Propranolol modulates the collateral vascular responsiveness to vasopressin via a Gα-mediated pathway in portal hypertensive rats
Jing-Yi Lee;
Jing-Yi Lee
*Institute of Pharmacology, National Yang-Ming University, No. 155, Sect. 2, Li-Nong St., Taipei 11221, Taiwan
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Teh-Ia Huo;
Teh-Ia Huo
*Institute of Pharmacology, National Yang-Ming University, No. 155, Sect. 2, Li-Nong St., Taipei 11221, Taiwan
†Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sect. 2, Shih-Pai Road, Taipei 11217, Taiwan
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Hui-Chun Huang;
†Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sect. 2, Shih-Pai Road, Taipei 11217, Taiwan
‡Faculty of Medicine, National Yang-Ming University, No. 155, Sect. 2, Li-Nong St., Taipei 11221, Taiwan
Correspondence: Dr Fa-Yauh Lee (email [email protected]) or Dr Hui-Chun Huang (email [email protected]).
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Fa-Yauh Lee;
‡Faculty of Medicine, National Yang-Ming University, No. 155, Sect. 2, Li-Nong St., Taipei 11221, Taiwan
§Department of Medicine, Taipei Veterans General Hospital, No. 201, Sect. 2, Shih-Pai Road, Taipei 11217, Taiwan
Correspondence: Dr Fa-Yauh Lee (email [email protected]) or Dr Hui-Chun Huang (email [email protected]).
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Han-Chieh Lin;
Han-Chieh Lin
†Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sect. 2, Shih-Pai Road, Taipei 11217, Taiwan
‡Faculty of Medicine, National Yang-Ming University, No. 155, Sect. 2, Li-Nong St., Taipei 11221, Taiwan
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Chiao-Lin Chuang;
Chiao-Lin Chuang
‡Faculty of Medicine, National Yang-Ming University, No. 155, Sect. 2, Li-Nong St., Taipei 11221, Taiwan
‖Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sect. 2, Shih-Pai Road, Taipei 11217, Taiwan
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Ching-Chih Chang;
Ching-Chih Chang
‡Faculty of Medicine, National Yang-Ming University, No. 155, Sect. 2, Li-Nong St., Taipei 11221, Taiwan
‖Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sect. 2, Shih-Pai Road, Taipei 11217, Taiwan
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Sun-Sang Wang;
Sun-Sang Wang
‡Faculty of Medicine, National Yang-Ming University, No. 155, Sect. 2, Li-Nong St., Taipei 11221, Taiwan
¶Department of Medical Affairs and Planning, Taipei Veterans General Hospital, No. 201, Sect. 2, Shih-Pai Road, Taipei 11217, Taiwan
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Shou-Dong Lee
Shou-Dong Lee
†Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sect. 2, Shih-Pai Road, Taipei 11217, Taiwan
‡Faculty of Medicine, National Yang-Ming University, No. 155, Sect. 2, Li-Nong St., Taipei 11221, Taiwan
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Publisher: Portland Press Ltd
Received:
December 06 2010
Revision Received:
June 16 2011
Accepted:
July 08 2011
Accepted Manuscript online:
July 08 2011
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2011 Biochemical Society
2011
Clin Sci (Lond) (2011) 121 (12): 545–554.
Article history
Received:
December 06 2010
Revision Received:
June 16 2011
Accepted:
July 08 2011
Accepted Manuscript online:
July 08 2011
Citation
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; Propranolol modulates the collateral vascular responsiveness to vasopressin via a Gα-mediated pathway in portal hypertensive rats. Clin Sci (Lond) 1 December 2011; 121 (12): 545–554. doi: https://doi.org/10.1042/CS20100590
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