| First Author | Tilley DG | Year | 2014 |
| Journal | Circulation | Volume | 130 |
| Issue | 20 | Pages | 1800-11 |
| PubMed ID | 25205804 | Mgi Jnum | J:234152 |
| Mgi Id | MGI:5789116 | Doi | 10.1161/CIRCULATIONAHA.114.010434 |
| Citation | Tilley DG, et al. (2014) beta-adrenergic receptor-mediated cardiac contractility is inhibited via vasopressin type 1A-receptor-dependent signaling. Circulation 130(20):1800-11 |
| abstractText | 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 beta-adrenergic receptor (betaAR) responsiveness. This led us to hypothesize that V1AR signaling regulates betaAR responsiveness and in doing so contributes to development of heart failure. METHODS AND RESULTS: Transaortic constriction resulted in decreased cardiac function and betaAR density and increased cardiac V1AR expression, effects reversed by a V1AR-selective antagonist. Molecularly, V1AR stimulation led to decreased betaAR ligand affinity, as well as betaAR-induced Ca(2+) mobilization and cAMP generation in isolated adult cardiomyocytes, effects recapitulated via ex vivo Langendorff analysis. V1AR-mediated regulation of betaAR 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 betaAR may be informative for the treatment of patients with acute decompensated heart failure and elevated arginine vasopressin. |
