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.