Research Communication Comparative effects of torasemide and furosemide on gap junction proteins and cardiac fibrosis in a rat model of dilated cardiomyopathy Kenichi Watanabe 1 * Remya Sreedhar 1 Rajarajan A. Thandavarayan 2 Vengadeshprabhu Karuppagounder 1 Vijayasree V. Giridharan 3 Shanish Antony 4 Meilei Harima 1 Masahiko Nakamura 5 Kenji Suzuki 6 Hiroshi Suzuki 1,7 Hirohito Sone 7 Somasundaram Arumugam 1 1 Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan 2 Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, USA 3 Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA 4 Department of Pharmacy, Government Medical College, Kottayam, Kerala, India 5 Department of Cardiology, Yamanashi Prefectural Central Hospital, Kofu, Yamanashi, Japan 6 Department of Gastroenterology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Japan 7 Department of Hematology, Endocrinology and Metabolism, Niigata University of Graduate School of Medicine and Dental Sciences, Niigata City, Japan Abstract Cardiac fibrosis is the major hallmark of adverse cardiac remod- eling in chronic heart failure (CHF) and its therapeutic targeting might help against cardiac dysfunction during chronic condi- tions. Diuretic agents are potentially useful in these cases, but their effects on the cardiac fibrosis pathogenesis are yet to be identified. This study was designed to identify and compare the effects of diuretic drugs torasemide and furosemide on cardiac fibrosis in a rat model of dilated cardiomyopathy induced by porcine cardiac myosin mediated experimental autoimmune myocarditis. Gap junction proteins, connexin-43 and N- cadherin, expressions were downregulated in the hearts of CHF rats, while torasemide treatment has upregulated their expres- sion. Western blotting and immunohistochemical analysis for various cardiac fibrosis related proteins as well as histopatho- logical studies have shown that both drugs have potential anti- fibrotic effects. Among them, torasemide has superior efficacy V C 2016 International Union of Biochemistry and Molecular Biology Volume 00, Number 00, Month/Month 2016, Pages 00–00 *Address for correspondence: Kenichi Watanabe, MD, PhD, Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City 956-8603, Japan. Tel.: 181 250255267; Fax.: 181 250255021; E-mail: watanabe@nupals.ac.jp. Received 17 June 2016; accepted 8 August 2016 DOI 10.1002/biof.1332 Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com) BioFactors 1