%0 Journal Article
%A Reboredo, Mercedes
%A Chang, Haisul C. Y.
%A Barbero, Roberto
%A Rodríguez Ortigosa, Carlos M.
%A Pérez Vizcaíno, Francisco
%A Morán, Asunción
%A García, Mónica
%A Banales, Jesus
%A Carreño, Norberto
%A Alegre, Félix
%A Herrero, Ignacio
%A Quiroga, Jorge
%A Prieto, Jesús
%A Sangro, Bruno
%T Zolmitriptan: A Novel Portal Hypotensive Agent WhichSynergizes with Propranolol in Lowering Portal Pressure
%D 2013
%@ 1932-6203
%U https://hdl.handle.net/20.500.14352/33274
%X Objective: Only a limited proportion of patients needing pharmacological control of portal hypertension are hemodynamicresponders to propranolol. Here we analyzed the effects of zolmitriptan on portal pressure and its potential interaction withpropranolol.Methods: Zolmitriptan, propranolol or both were tested in two rat models of portal hypertension: common bile ductligation (CBDL) and CCl4-induced cirrhosis. In these animals we measured different hemodynamic parameters includingportal venous pressure, arterial renal flow, portal blood flow and cardiac output. We also studied the changes in superiormesenteric 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 pressureaccompanied by reduction of portal flow with only slight decrease in renal flow. In cirrhotic rats, splanchnic sympathectomyintensified and prolonged zolmitriptan-induced portal pressure descent. Also, propranolol caused more intense and durableportal pressure fall when combined with zolmitriptan. Mesenteric artery perfusion pressure peaked for about 1 min uponzolmitriptan administration but showed no change with propranolol. However propranolol enhanced and prolonged theelevation in mesenteric artery perfusion pressure induced by zolmitriptan. In vitro studies showed that propranololprevented the inhibitory effects of b2-agonists on zolmitriptan-induced vasoconstriction and the combination ofpropranolol 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
%~