OVEREXPRESSION OF ANGIOTENSIN AT(1) RECEPTOR TRANSGENE IN THE MOUSE MYOCARDIUM PRODUCES A LETHAL PHENOTYPE ASSOCIATED WITH MYOCYTE HYPERPLASIA AND HEART-BLOCK

Previous studies have suggested that angiotensin II (Ang II) modulates cardiac contractility, rhythm, metabolism, and structure, However, it is unclear whether the cardiac effects are due to direct actions of A ng II on the myocardium or if they are due to secondary effects mediat ed through the hemodynamic actions of Ang II, In this study, we used t he alpha-myosin heavy chain (alpha MHC) promoter to generate transgeni c mice overexpressing angiotensin II type 1 (AT(1a)) receptor selectiv ely in cardiac myocytes, The specificity of transgene expression in th e transgenic offspring was confirmed by radioligand binding studies an d reverse transcription-PCR, The offspring displayed massive atrial en largement with myocyte hyperplasia at birth, developed significant bra dycardia with heart block, and died within the first weeks after birth , Thus, direct activation of AT(1) receptor signaling in cardiac myocy tes in vivo is sufficient to induce cardiac myocyte growth and alter e lectrical conduction.