Cardiac hypertrophy and altered beta-adrenergic signaling in transgenic mice that express the amino terminus of beta-ARK1.

The G protein-coupled receptor (GPCR) kinase beta-adrenergic receptor (beta-AR) kinase-1 (beta-ARK1) is elevated during heart failure; however, its role is not fully understood. Beta-ARK1 contains several domains that are capable of protein-protein interactions that may play critical roles in the regulation of GPCR signaling. In this study, we developed a novel line of transgenic mice that express an amino-terminal peptide of beta-ARK1 that is comprised of amino acid residues 50-145 (beta-ARKnt) in the heart to determine whether this domain has any functional significance in vivo.

Gq-coupled receptor agonists mediate cardiac hypertrophy via the vasculature.

The Gq-coupled receptor-signaling pathway has been implicated in the cardiac hypertrophic response to stress, but little is actually known about the contributions of Gq signaling in either the heart or the vasculature. Therefore, we developed a line of transgenic mice that express a peptide inhibitor of Gq (GqI) in vascular smooth muscle to determine if vascular Gq signaling was important in the cardiac hypertrophic response. After chronic administration of the Gq agonists phenylephrine, serotonin, and angiotensin II, we observed an attenuation of mean arterial blood pressure and an inhibition of cardiac hypertrophy in the transgenic mice with vascular-specific GqI expression.