?-adrenergic receptor-mediated cardiac contractility is inhibited via vasopressin type 1A-receptor-dependent signaling.

ABSTRACT: 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 ?-adrenergic receptor (?AR) responsiveness. This led us to hypothesize that V1AR signaling regulates ?AR responsiveness and in doing so contributes to development of heart failure.Transaortic constriction resulted in decreased cardiac function and ?AR density and increased cardiac V1AR expression, effects reversed by a V1AR-selective antagonist. Molecularly, V1AR stimulation led to decreased ?AR ligand affinity, as well as ?AR-induced Ca(2+) mobilization and cAMP generation in isolated adult cardiomyocytes, effects recapitulated via ex vivo Langendorff analysis. V1AR-mediated regulation of ?AR responsiveness was demonstrated to occur in a previously unrecognized Gq protein-independent/G protein receptor kinase-dependent manner.This newly discovered relationship between cardiac V1AR and ?AR may be informative for the treatment of patients with acute decompensated heart failure and elevated arginine vasopressin.

SUBMITTER: Tilley DG 

PROVIDER: S-EPMC4229385 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature