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1 Anesthesiology, Clinical Research and Development, University of Colorado at Denver and Health Sciences Center, Denver, Colorado, United States; Department of Anesthesiology and Intensive Care Medicine, University of Leipzig Medical Faculty, Leipzig, Germany
2 Anesthesiology, Clinical Research and Development, University of Colorado at Denver and Health Sciences Center, Denver, Colorado, United States
3 Anesthesiology, Clinical Research and Development, University of Colorado at Denver and Health Sciences Center, Denver, Colorado, United States; Transplantation Surgery, Charite - Universitaetsmedizin Berlin, Berlin, Berlin, Germany
4 Center for Genetic Lung Disease, University of Colorado at Denver and Health Sciences Center, Denver, Colorado, United States
5 Division of Pulmonary Sciences and Critical Care Medicine, Cardiovascular Research Laboratory, University of Colorado at Denver and Health Sciences Center, Denver, Colorado, United States
6 Anesthesiology, VU University Medical Center, Amsterdam, Netherlands
7 Department of Anesthesiology and Intensive Care Medicine, University of Leipzig Medical Faculty, Leipzig, Germany
8 Anesthesiology and Critical Care, Harvard Medical School at Massachusetts General Hospital, Boston, Massachusetts, United States
* To whom correspondence should be addressed. E-mail: wsteudel{at}partners.org.
HMG-CoA-reductase inihibitors (statins) influence lipid metabolism and have pleiotropic effects. Several statins reduce various forms of pulmonary hypertension (PH) in animal models. The effect of atorvastatin has, to our knowledge, not been studied in the context of PH. 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. Methods: 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 week 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 week course, invasive right ventricular pressure, right ventricular weight, quantitative morphology and 5-HTT expression were measured. Results: 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 week course. MCT challenge was associated with increased pulmonary vascular 5-HTT expression, and atorvastatin treatment reduced the 5-HTT expression. Conclusions: MCT-induced PH over the course of 4 weeks 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.
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