title: Serotonin transporter protein in pulmonary hypertensive rats treated with atorvastatin.
abstract: HMG-CoA-reductase inhibitors (statins) influence lipid metabolism and have pleiotropic effects. Several statins reduce various forms of pulmonary hypertension (PH) in animal models. The relationship between atorvastatin and expression of serotonin transporter protein (5-HTT) remains unknown. This study focused on the effects of atorvastatin on the course of monocrotaline (MCT)-induced PH and its relation to 5-HTT expression. Male Sprague-Dawley rats were challenged with MCT with or without subsequent daily oral treatment with 0.1, 1, and 10 mg/kg of atorvastatin for 28 days. Over the 4-wk course, the progression of PH was followed by transthoracic echocardiography [pulmonary artery pressure was assessed by pulmonary artery flow acceleration time (PAAT), an estimate reciprocal to pulmonary artery pressure], and, at the end of the 4-wk course, invasive right ventricular pressure, right ventricular weight, quantitative morphology, and 5-HTT expression were measured. MCT caused significant PH as early as 7 days after injection. Atorvastatin treatment increased PAAT and reduced right ventricular pressure, right ventricular hypertrophy, and vascular remodeling over the 4-wk course. MCT challenge was associated with increased pulmonary vascular 5-HTT expression, and atorvastatin treatment reduced the 5-HTT expression. MCT-induced PH over the course of 4 wk can be easily followed by transthoracic echocardiography, and atorvastatin is effective in reducing the PH. Atorvastatin's effects are associated with a decrease of 5-HTT expression.
authors.affiliation: Department of Anesthesiology, Clinical Research and Development, University of Colorado at Denver and Health Sciences Center, Denver, Colorado, USA.
authors.forename: Sven
authors.initials: S
authors.lastname: Laudi
authors.forename: Saskia
authors.initials: S
authors.lastname: Trump
authors.forename: Volker
authors.initials: V
authors.lastname: Schmitz
authors.forename: James
authors.initials: J
authors.lastname: West
authors.forename: Ivan F
authors.initials: IF
authors.lastname: McMurtry
authors.forename: Haitham
authors.initials: H
authors.lastname: Mutlak
authors.forename: Uwe
authors.initials: U
authors.lastname: Christians
authors.forename: Jörg
authors.initials: J
authors.lastname: Weimann
authors.forename: Udo
authors.initials: U
authors.lastname: Kaisers
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Steudel
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000069059:Atorvastatin; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D005786:Gene Expression Regulation / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D016133:Polymerase Chain Reaction; D011651:Pulmonary Artery / Q000187:drug effects; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D013599:Systole / Q000187:drug effects
chemical_list: D000199:Actins; D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D012333:RNA, Messenger; D050486:Serotonin Plasma Membrane Transport Proteins; D000069059:Atorvastatin