S Sakai1, T Miyauchi, I Yamaguchi. 1. Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Abstract
BACKGROUND: We reported that long-term (3-month) treatment with the endothelin (ET) type A (ET(A)) receptor antagonist BQ-123 markedly improved survival in rats with chronic heart failure (CHF). However, it is not known whether long-term treatment with an ET receptor antagonist improves alterations in the expression of cardiac genes in failing hearts. METHODS AND RESULTS: CHF rats and control sham-operated rats were treated with BQ-123, SB209670 (ET(A/B) dual receptor antagonist), or saline (vehicle) for 3 months. The survival of CHF rats was markedly higher in the BQ-123 or SB209670 treatment group than in the saline treatment group. The changes in the gene expression of classic molecular markers for failing hearts (mRNA levels of atrial natriuretic peptide and beta-myosin heavy chain) were greatly inhibited by BQ-123 or SB209670 treatment in CHF rats. Long-term BQ-123 treatment also normalized the alterations in the expression of functional molecular markers in failing hearts (eg, mRNA levels of ryanodine receptor, sarcoplasmic reticulum Ca(2+)-ATPase, angiotensin-converting enzyme, angiotensin II type 1 receptor, and prepro-ET-1). CONCLUSIONS: We demonstrated for the first time that long-term (3-month) treatment with an ET receptor antagonist improves the alterations in the expression of various cardiac genes of classic molecular markers (eg, mRNA in atrial natriuretic peptide and beta-myosin heavy chain) and of functional molecular markers (eg, mRNA levels of ryanodine receptor, sarcoplasmic reticulum Ca(2+)-ATPase, angiotensin-converting enzyme, angiotensin II type 1 receptor, and prepro-ET-1) in the failing hearts of CHF rats, suggesting that the great improvement of survival in CHF rats by an ET blocker is partly attributed to the prevention of molecular changes in failing hearts.
BACKGROUND: We reported that long-term (3-month) treatment with the endothelin (ET) type A (ET(A)) receptor antagonist BQ-123 markedly improved survival in rats with chronic heart failure (CHF). However, it is not known whether long-term treatment with an ET receptor antagonist improves alterations in the expression of cardiac genes in failing hearts. METHODS AND RESULTS:CHFrats and control sham-operated rats were treated with BQ-123, SB209670 (ET(A/B) dual receptor antagonist), or saline (vehicle) for 3 months. The survival of CHFrats was markedly higher in the BQ-123 or SB209670 treatment group than in the saline treatment group. The changes in the gene expression of classic molecular markers for failing hearts (mRNA levels of atrial natriuretic peptide and beta-myosin heavy chain) were greatly inhibited by BQ-123 or SB209670 treatment in CHFrats. Long-term BQ-123 treatment also normalized the alterations in the expression of functional molecular markers in failing hearts (eg, mRNA levels of ryanodine receptor, sarcoplasmic reticulum Ca(2+)-ATPase, angiotensin-converting enzyme, angiotensin II type 1 receptor, and prepro-ET-1). CONCLUSIONS: We demonstrated for the first time that long-term (3-month) treatment with an ET receptor antagonist improves the alterations in the expression of various cardiac genes of classic molecular markers (eg, mRNA in atrial natriuretic peptide and beta-myosin heavy chain) and of functional molecular markers (eg, mRNA levels of ryanodine receptor, sarcoplasmic reticulum Ca(2+)-ATPase, angiotensin-converting enzyme, angiotensin II type 1 receptor, and prepro-ET-1) in the failing hearts of CHFrats, suggesting that the great improvement of survival in CHFrats by an ET blocker is partly attributed to the prevention of molecular changes in failing hearts.
Authors: Mohamed Y Abd El Rahman; Axel Rentzsch; Philipp Scherber; Siegrun Mebus; Oliver Miera; Günther Balling; Petra Böttler; Karl-Otto Dubowy; Birgit Farahwaschy; Alfred Hager; Joachim Kreuder; Brigitte Peters; Felix Berger; Ingram Schulze-Neick; Hashim Abdul-Khaliq Journal: Clin Res Cardiol Date: 2014-03-30 Impact factor: 5.460
Authors: Herbert B Tanowitz; Huan Huang; Linda A Jelicks; Madhulika Chandra; Maria L Loredo; Louis M Weiss; Stephen M Factor; Vitaliy Shtutin; Shankar Mukherjee; Richard N Kitsis; George J Christ; Murray Wittner; Jamshid Shirani; Yaz Y Kisanuki; Masashi Yanagisawa Journal: Infect Immun Date: 2005-04 Impact factor: 3.441