10.25376/hra.7819970.v1 Douglas G. Tilley Douglas G. Tilley Weizhong Zhu Weizhong Zhu Vaerie D. Myers Vaerie D. Myers Larry A. Barr Larry A. Barr Erhe Gao Erhe Gao Jianliang Song Jianliang Song Rhonda L. Carter Rhonda L. Carter Catherine A. Makarewich Catherine A. Makarewich Daohai Yu Daohai Yu Constantine D. Troupes Constantine D. Troupes Laurel A. Grisanti Laurel A. Grisanti Ryan C. Coleman Ryan C. Coleman Walter J. Koch Walter J. Koch Steven R. Houser Steven R. Houser Joseph Y. Cheung Joseph Y. Cheung Arthur M. Feldman Arthur M. Feldman Beta-adrenergic receptor-mediated cardiac contractility is inhibited via vasopressin type 1A-receptor-dependent signaling.pdf Health Research Alliance 2019 Cardiomyopathies Myocardial failure Myocardium Receptors, adrenergic, beta vassopressin type 1A receptor Cardiology (incl. Cardiovascular Diseases) 2019-03-08 14:03:14 Journal contribution https://hra.figshare.com/articles/journal_contribution/Beta-adrenergic_receptor-mediated_cardiac_contractility_is_inhibited_via_vasopressin_type_1A-receptor-dependent_signaling_pdf/7819970 Background—Enhanced arginine vasopressin levels are associated with increased mortality during end-stage human heart failure, and cardiac arginine vasopressin type 1A receptor (V1AR) expression becomes increased. Additionally, mice with cardiac-restricted V1AR overexpression develop cardiomyopathy and decreased β-adrenergic receptor (βAR) responsiveness. This led us to hypothesize that V1AR signaling regulates βAR responsiveness and in doing so contributes to development of heart failure. Methods and Results—Transaortic constriction resulted in decreased cardiac function and βAR density and increased cardiac V1AR expression, effects reversed by a V1AR-selective antagonist. Molecularly, V1AR stimulation led to decreased βAR ligand affinity, as well as βAR-induced Ca2+ mobilization and cAMP generation in isolated adult cardiomyocytes, effects recapitulated via ex vivo Langendorff analysis. V1AR-mediated regulation of βAR responsiveness was demonstrated to occur in a previously unrecognized Gq protein–independent/G protein receptor kinase–dependent manner. Conclusions—This newly discovered relationship between cardiac V1AR and βAR may be informative for the treatment of patients with acute decompensated heart failure and elevated arginine vasopressin.