α-Adrenergic Signal Transduction in Renin Transgenic Rats

Abstract The α1-adrenoceptor–G protein–phosphoinositide-specific phospholipase C (PLC) signal transduction pathway is assumed to play an important role in the regulation of contractile force and in the pathophysiology of myocardial hypertrophy. In the present study, the components of this pathway were investigated in left ventricles of hearts from hypertensive transgenic rats overexpressing the mouse renin gene [TG(mREN2)27] in comparison to age- and weight-matched Sprague-Dawley control rats. Contractile force was assessed in isolated electrically driven left ventricular papillary muscle strips. α1-adrenoceptor density was measured by radioligand binding using [3H]prazosin, steady state levels of αq/11, and G protein β-subunits by Western blotting. PLC activity was determined by a cell-free assay using exogenous phospholipid vesicles containing [3H]phosphatidylinositol (4,5)-bisphosphate as a substrate. α1-Adrenoceptor density was significantly increased (by 80%) in transgenic rats compared with control ...