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Zolmitriptan: A Novel Portal Hypotensive Agent Which Synergizes with Propranolol in Lowering Portal Pressure

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Reboredo, Mercedes and Chang, Haisul C. Y. and Barbero, Roberto and Rodríguez Ortigosa, Carlos M. and Pérez Vizcaíno, Francisco and Morán, Asunción and García, Mónica and Banales, Jesus and Carreño, Norberto and Alegre, Félix and Herrero, Ignacio and Quiroga, Jorge and Prieto, Jesús and Sangro, Bruno (2013) Zolmitriptan: A Novel Portal Hypotensive Agent Which Synergizes with Propranolol in Lowering Portal Pressure. Plos One, 8 (1). e52683-e52683. ISSN 1932-6203

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Abstract

Objective: Only a limited proportion of patients needing pharmacological control of portal hypertension are hemodynamic
responders to propranolol. Here we analyzed the effects of zolmitriptan on portal pressure and its potential interaction with
propranolol.
Methods: Zolmitriptan, propranolol or both were tested in two rat models of portal hypertension: common bile duct
ligation (CBDL) and CCl4-induced cirrhosis. In these animals we measured different hemodynamic parameters including
portal venous pressure, arterial renal flow, portal blood flow and cardiac output. We also studied the changes in superior
mesenteric artery perfusion pressure and in arterial wall cAMP levels induced by zolmitriptan, propranolol or both.
Moreover, we determined the effect of splanchnic sympathectomy on the response of PVP to zolmitriptan.
Results: In both models of portal hypertension zolmitriptan induced a dose-dependent transient descent of portal pressure
accompanied by reduction of portal flow with only slight decrease in renal flow. In cirrhotic rats, splanchnic sympathectomy
intensified and prolonged zolmitriptan-induced portal pressure descent. Also, propranolol caused more intense and durable
portal pressure fall when combined with zolmitriptan. Mesenteric artery perfusion pressure peaked for about 1 min upon
zolmitriptan administration but showed no change with propranolol. However propranolol enhanced and prolonged the
elevation in mesenteric artery perfusion pressure induced by zolmitriptan. In vitro studies showed that propranolol
prevented the inhibitory effects of b2-agonists on zolmitriptan-induced vasoconstriction and the combination of
propranolol and zolmitriptan significantly reduced the elevation of cAMP caused by b2-agonists.
Conclusion: Zolmitriptan reduces portal hypertension and non-selective beta-blockers can improve this effect. Combinatio


Item Type:Article
Uncontrolled Keywords:Zolmitriptan, Portal hypertension
Subjects:Medical sciences > Medicine > Pharmacology
ID Code:20432
Deposited On:14 Mar 2013 11:53
Last Modified:07 Feb 2014 10:13

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