Zolmitriptan: A Novel Portal Hypotensive Agent Which Synergizes with Propranolol in Lowering Portal Pressure
Publication Date
January 16, 2013
Journal
PLOS ONE
Authors
Mercedes Reboredo, Haisul C. Y. Chang, Roberto Barbero, Carlos M. Rodríguez Ortigosa, et al
Volume
8
Issue
1
Pages
e52683
DOI
https://dx.plos.org/10.1371/journal.pone.0052683
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0052683
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/23341903
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547109
Europe PMC
http://europepmc.org/abstract/MED/23341903
Web of Science
000313682700013
Scopus
84872459028
Mendeley
http://www.mendeley.com/research/zolmitriptan-novel-portal-hypotensive-agent-synergizes-propranolol-lowering-portal-pressure
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Mendeley | Further Information

{"title"=>"Zolmitriptan: A Novel Portal Hypotensive Agent Which Synergizes with Propranolol in Lowering Portal Pressure", "type"=>"journal", "authors"=>[{"first_name"=>"Mercedes", "last_name"=>"Reboredo", "scopus_author_id"=>"6701762183"}, {"first_name"=>"Haisul C.Y.", "last_name"=>"Chang", "scopus_author_id"=>"53871036400"}, {"first_name"=>"Roberto", "last_name"=>"Barbero", "scopus_author_id"=>"55559316000"}, {"first_name"=>"Carlos M.", "last_name"=>"Rodríguez-Ortigosa", "scopus_author_id"=>"6602745536"}, {"first_name"=>"Francisco", "last_name"=>"Pérez-Vizcaíno", "scopus_author_id"=>"7004744225"}, {"first_name"=>"Asunción", "last_name"=>"Morán", "scopus_author_id"=>"7201919610"}, {"first_name"=>"Mónica", "last_name"=>"García", "scopus_author_id"=>"57198924673"}, {"first_name"=>"Jesús M.", "last_name"=>"Banales", "scopus_author_id"=>"55883170600"}, {"first_name"=>"Norberto", "last_name"=>"Carreño", "scopus_author_id"=>"56253102000"}, {"first_name"=>"Félix", "last_name"=>"Alegre", "scopus_author_id"=>"23987239600"}, {"first_name"=>"Ignacio", "last_name"=>"Herrero", "scopus_author_id"=>"7003953829"}, {"first_name"=>"Jorge", "last_name"=>"Quiroga", "scopus_author_id"=>"7102063176"}, {"first_name"=>"Jesús", "last_name"=>"Prieto", "scopus_author_id"=>"55701746900"}, {"first_name"=>"Bruno", "last_name"=>"Sangro", "scopus_author_id"=>"7004456732"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"23341903", "sgr"=>"84872459028", "pui"=>"368133756", "scopus"=>"2-s2.0-84872459028", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "doi"=>"10.1371/journal.pone.0052683"}, "id"=>"f23bcb80-d311-3aa4-9b8f-6d6a6ee7ec9e", "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.\\n\\nMETHODS: 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.\\n\\nRESULTS: 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 β2-agonists on zolmitriptan-induced vasoconstriction and the combination of propranolol and zolmitriptan significantly reduced the elevation of cAMP caused by β2-agonists.\\n\\nCONCLUSION: Zolmitriptan reduces portal hypertension and non-selective beta-blockers can improve this effect. Combination therapy deserves consideration for patients with portal hypertension failing to respond to non-selective beta-blockers.", "link"=>"http://www.mendeley.com/research/zolmitriptan-novel-portal-hypotensive-agent-synergizes-propranolol-lowering-portal-pressure", "reader_count"=>11, "reader_count_by_academic_status"=>{"Researcher"=>1, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Researcher"=>1, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Medicine and Dentistry"=>8, "Neuroscience"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Psychology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Neuroscience"=>{"Neuroscience"=>1}, "Psychology"=>{"Psychology"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Spain"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/506147"], "description"=>"<p>Measurement of arterial pressure (MAP) (A), cardiac output (CO) (B) and systemic vascular resistance (SVR) (C) after zolmitriptan, terlipressin or saline administration. (D) Effect of chronic administration of zolmitriptan in portal pressure (PVP). */**p<0.05/0.01 vs saline.</p>", "links"=>[], "tags"=>["zolmitriptan", "terlipressin"], "article_id"=>176646, "categories"=>["Marine Biology", "Chemistry", "Mental Health", "Pharmacology"], "users"=>["Mercedes Reboredo", "Haisul C. Y. Chang", "Roberto Barbero", "Carlos M. Rodríguez-Ortigosa", "Francisco Pérez-Vizcaíno", "Asunción Morán", "Mónica García", "Jesús M. Banales", "Norberto Carreño", "Félix Alegre", "Ignacio Herrero", "Jorge Quiroga", "Jesús Prieto", "Bruno Sangro"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0052683.g002", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Systemic_and_chronic_effects_of_zolmitriptan_and_terlipressin_in_CBDL_rats_/176646", "title"=>"Systemic and chronic effects of zolmitriptan and terlipressin in CBDL-rats.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-16 01:50:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/506866"], "description"=>"<p>Values of body weight and biochemical variables are expressed as median and ranges and hemodynamic data are expressed as mean±SEM. ALP: alkaline phosphatase, ALT: alanine transaminase, AST: aspartate aminotransferase, PVP: portal vein pressure.</p>", "links"=>[], "tags"=>["biochemical", "basal", "hemodynamic", "parameters", "rats", "portal", "hypertension", "received", "infusion", "terlipressin"], "article_id"=>177352, "categories"=>["Marine Biology", "Chemistry", "Mental Health", "Pharmacology"], "users"=>["Mercedes Reboredo", "Haisul C. Y. Chang", "Roberto Barbero", "Carlos M. Rodríguez-Ortigosa", "Francisco Pérez-Vizcaíno", "Asunción Morán", "Mónica García", "Jesús M. Banales", "Norberto Carreño", "Félix Alegre", "Ignacio Herrero", "Jorge Quiroga", "Jesús Prieto", "Bruno Sangro"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0052683.t001", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Body_weight_biochemical_data_and_basal_hemodynamic_parameters_of_rats_with_portal_hypertension_which_received_i_v_infusion_of_zolmitriptan_terlipressin_or_saline_/177352", "title"=>"Body weight, biochemical data and basal hemodynamic parameters of rats with portal hypertension which received i.v. infusion of zolmitriptan, terlipressin or saline.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-01-16 02:02:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/276265", "https://ndownloader.figshare.com/files/276313", "https://ndownloader.figshare.com/files/276372", "https://ndownloader.figshare.com/files/276415"], "description"=>"<div><h3>Objective</h3><p>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.</p> <h3>Methods</h3><p>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.</p> <h3>Results</h3><p>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. <em>In vitro</em> studies showed that propranolol prevented the inhibitory effects of β2-agonists on zolmitriptan-induced vasoconstriction and the combination of propranolol and zolmitriptan significantly reduced the elevation of cAMP caused by β2-agonists.</p> <h3>Conclusion</h3><p>Zolmitriptan reduces portal hypertension and non-selective beta-blockers can improve this effect. Combination therapy deserves consideration for patients with portal hypertension failing to respond to non-selective beta-blockers.</p> </div>", "links"=>[], "tags"=>["portal", "hypotensive", "synergizes", "propranolol", "lowering", "pressure"], "article_id"=>114448, "categories"=>["Marine Biology", "Chemistry", "Mental Health", "Pharmacology"], "users"=>["Mercedes Reboredo", "Haisul C. Y. Chang", "Roberto Barbero", "Carlos M. Rodríguez-Ortigosa", "Francisco Pérez-Vizcaíno", "Asunción Morán", "Mónica García", "Jesús M. Banales", "Norberto Carreño", "Félix Alegre", "Ignacio Herrero", "Jorge Quiroga", "Jesús Prieto", "Bruno Sangro"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0052683.s001", "https://dx.doi.org/10.1371/journal.pone.0052683.s002", "https://dx.doi.org/10.1371/journal.pone.0052683.s003", "https://dx.doi.org/10.1371/journal.pone.0052683.s004"], "stats"=>{"downloads"=>27, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Zolmitriptan_A_Novel_Portal_Hypotensive_Agent_Which_Synergizes_with_Propranolol_in_Lowering_Portal_Pressure__/114448", "title"=>"Zolmitriptan: A Novel Portal Hypotensive Agent Which Synergizes with Propranolol in Lowering Portal Pressure", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-01-16 01:14:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/506641"], "description"=>"<p>(A,B) Zolmitriptan alone or in combination with propranolol, atenolol and ICI-118,551 were administered intra-arterially and perfusion pressure recorded. (C) <i>In vitro</i> mesenteric artery contraction studies after zolmitriptan and propranolol administration in the presence or absence of isoproterenol. (D) cAMP measurement in mesenteric artery wall after administration of zolmitriptan, propranolol or the combination or both in the presence of isoproterenol. */*p<0.05 vs control group/group receiving only isoproterenol.</p>", "links"=>[], "tags"=>["zolmitriptan", "beta-blockers", "splanchnic", "vasculature"], "article_id"=>177138, "categories"=>["Marine Biology", "Chemistry", "Mental Health", "Pharmacology"], "users"=>["Mercedes Reboredo", "Haisul C. Y. Chang", "Roberto Barbero", "Carlos M. Rodríguez-Ortigosa", "Francisco Pérez-Vizcaíno", "Asunción Morán", "Mónica García", "Jesús M. Banales", "Norberto Carreño", "Félix Alegre", "Ignacio Herrero", "Jorge Quiroga", "Jesús Prieto", "Bruno Sangro"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0052683.g005", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_zolmitriptan_in_combination_with_beta_blockers_on_splanchnic_vasculature_of_healthy_rats_/177138", "title"=>"Effects of zolmitriptan in combination with beta-blockers on splanchnic vasculature of healthy rats.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-16 01:58:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/506479"], "description"=>"<p>Propranolol or nadolol were administered as an intravenous infusion and 5 minutes later, zolmitriptan or saline infusion were started and portal pressure (PVP) (A,C) and heart rate (HR) (B,D) recorded. Infusion time is indicated with black (beta-blockers) and grey bars (zolmitriptan). */* indicates significance vs rats receiving only NSBB (p<0.05/0.01).</p>", "links"=>[], "tags"=>["zolmitriptan", "nsbb", "ccl4-treated"], "article_id"=>176983, "categories"=>["Marine Biology", "Chemistry", "Mental Health", "Pharmacology"], "users"=>["Mercedes Reboredo", "Haisul C. Y. Chang", "Roberto Barbero", "Carlos M. Rodríguez-Ortigosa", "Francisco Pérez-Vizcaíno", "Asunción Morán", "Mónica García", "Jesús M. Banales", "Norberto Carreño", "Félix Alegre", "Ignacio Herrero", "Jorge Quiroga", "Jesús Prieto", "Bruno Sangro"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0052683.g004", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_zolmitriptan_in_combination_NSBB_in_CCl4_treated_rats_/176983", "title"=>"Effect of zolmitriptan in combination NSBB in CCl4-treated rats.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-16 01:56:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/506327"], "description"=>"<p>(A) Portal pressure (PVP). (B) Renal flow (ARF). (C) Portal flow (PBF). (D) Portal pressure after SS. */** significance vs saline or sham p<0.05/0.01.</p>", "links"=>[], "tags"=>["intravenous", "infusion", "zolmitriptan", "ccl4-treated"], "article_id"=>176826, "categories"=>["Marine Biology", "Chemistry", "Mental Health", "Pharmacology"], "users"=>["Mercedes Reboredo", "Haisul C. Y. Chang", "Roberto Barbero", "Carlos M. Rodríguez-Ortigosa", "Francisco Pérez-Vizcaíno", "Asunción Morán", "Mónica García", "Jesús M. Banales", "Norberto Carreño", "Félix Alegre", "Ignacio Herrero", "Jorge Quiroga", "Jesús Prieto", "Bruno Sangro"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0052683.g003", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_intravenous_infusion_of_zolmitriptan_in_CCl4_treated_rats_/176826", "title"=>"Effect of intravenous infusion of zolmitriptan in CCl4-treated rats.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-16 01:53:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/505983"], "description"=>"<p>(A,C) Portal pressure (PVP). (B,D) Renal flow (ARF). *p<0.05 vs saline. */**p<0.05/0.01 vs zolmitriptan dose 10 mg/kg.</p>", "links"=>[], "tags"=>["intravenous", "infusion", "zolmitriptan", "terlipressin"], "article_id"=>176476, "categories"=>["Marine Biology", "Chemistry", "Mental Health", "Pharmacology"], "users"=>["Mercedes Reboredo", "Haisul C. Y. Chang", "Roberto Barbero", "Carlos M. Rodríguez-Ortigosa", "Francisco Pérez-Vizcaíno", "Asunción Morán", "Mónica García", "Jesús M. Banales", "Norberto Carreño", "Félix Alegre", "Ignacio Herrero", "Jorge Quiroga", "Jesús Prieto", "Bruno Sangro"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0052683.g001", "stats"=>{"downloads"=>1, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_intravenous_infusion_of_zolmitriptan_and_terlipressin_in_CBDL_rats_/176476", "title"=>"Effect of intravenous infusion of zolmitriptan and terlipressin in CBDL-rats.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-16 01:47:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/506803"], "description"=>"<p>Data are expressed as mean±SEM. <sub>a</sub> compared to the vehicle group, p<0.05.</p>", "links"=>[], "tags"=>["hemodynamic", "parameters", "cbdl", "rats", "zolmitriptan"], "article_id"=>177306, "categories"=>["Marine Biology", "Chemistry", "Mental Health", "Pharmacology"], "users"=>["Mercedes Reboredo", "Haisul C. Y. Chang", "Roberto Barbero", "Carlos M. Rodríguez-Ortigosa", "Francisco Pérez-Vizcaíno", "Asunción Morán", "Mónica García", "Jesús M. Banales", "Norberto Carreño", "Félix Alegre", "Ignacio Herrero", "Jorge Quiroga", "Jesús Prieto", "Bruno Sangro"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0052683.t002", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Biochemical_data_and_hemodynamic_parameters_in_CBDL_rats_after_chronic_treatment_with_zolmitriptan_or_vehicle_/177306", "title"=>"Biochemical data and hemodynamic parameters in CBDL rats after chronic treatment with zolmitriptan or vehicle.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-01-16 02:01:46"}

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Relative Metric

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