Effects of simvastatin on pulmonary fibrosis, pulmonary hypertension and exercise capacity in bleomycin‐treated rats. (25th March 2013)

• Record Type: Journal Article
• Authors: Schroll, S.; Lange, T. J.; Arzt, M.; Sebah, D.; Nowrotek, A.; Lehmann, H.; Wensel, R.; Pfeifer, M.; Blumberg, F. C.
• Is Part Of: Acta physiologica. Volume 208:Number 2(2013:Jun.)
• Page Start: 191
• Page End: 201
• Publication Date: 2013-03-25
• Subjects: Physiology -- Periodicals; Physiology -- Research -- Periodicals; 612
• DOI: 10.1111/apha.12085
• Languages: English
• ISSNs: 1748-1708

Abstract

<abstract abstract-type="main" xml:lang="en" id="apha12085-abs-0001"> <title>Abstract</title> <sec id="apha12085-sec-0001" sec-type="section"> <title>Aim</title> <p>Pulmonary fibrosis is often complicated by pulmonary hypertension. Statins reduce fibroblast activity <italic>in vitro</italic> and pulmonary hypertension <italic>in vivo</italic>. We investigated whether Simvastatin exerts beneficial effects on pulmonary fibrosis and pulmonary hypertension in Bleomycin‐treated rats <italic>in vivo</italic>.</p> </sec> <sec id="apha12085-sec-0002" sec-type="section"> <title>Methods</title> <p>Rats were randomly assigned to controls, Bleomycin, Bleomycin plus Simvastatin from day 1 to 28 and Bleomycin plus Simvastatin from day 13 to 28. 28 days after Bleomycin instillation, right ventricular systolic pressure (RVSP), right ventricular mass (RV/(LV+S)), right ventricular and circulating brain natriuretic peptide (BNP) levels were determined to assess pulmonary hypertension. Pulmonary hydroxyproline content (HPC), pulmonary connective tissue growth factor (CTGF) transcription and lung compliance (LC) were analysed to characterize pulmonary fibrosis. Exercise capacity was determined by treadmill tests.</p> </sec> <sec id="apha12085-sec-0003" sec-type="section"> <title>Results</title> <p>Compared with controls, Bleomycin increased RVSP, RV/(LV+S), BNP levels, HPC and CTGF transcription and decreased LC significantly. Simvastatin administered from day 1 to 28 normalized all these parameters. Simvastatin administered from day 13 to 28 had no effect on HPC and LC, but reduced RV/(LV+S) significantly and induced a strong trend to lower RVSP and BNP levels. Exercise capacity was reduced by Bleomycin. Simvastatin significantly improved exercise intolerance in both treatment groups.</p> </sec> <sec id="apha12085-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Simvastatin prevents the development of pulmonary fibrosis, but fails to attenuate already established pulmonary fibrosis. In contrast, it ameliorates pulmonary hypertension and thereby exercise capacity in the prevention and the treatment group regardless of its effects on pulmonary fibrosis. Whether statins are a treatment option in humans with pulmonary fibrosis needs to be investigated by further study.</p> </sec> </abstract>