Zolk O. Chamber-specific alterations of norepinephrine uptake sites in cardiac hypertrophy. Hypertension 32: 831–837

Abstract—The present study investigated local differences of sympathetic activation and sympathetic neuroeffector defects in nonhypertrophied right and hypertrophied left ventricles in a rat model with renin-induced pressure overload [TG(mREN2)27]. As judged from the depletion of myocardial norepinephrine stores, sympathetic activation was more pronounced in the left than in the right ventricles. In addition, norepinephrine uptake1 carrier sites were reduced in left but unchanged in right ventricles. Gene expression of the carrier was unchanged in stellate ganglia. An increase of Gia expression and a heterologous adenylyl cyclase desensitization occurred only in the left but not in the right ventricles, whereas a reduction of b-adrenergic receptors was observed in both chambers. We concluded that general sympathetic activation can lead to b-adrenoceptor downregulation but that pressure overload further increases sympathetic activation involving norepinephrine uptake mechanisms in the left ventricles, resulting in heterologous b-adrenergic desensitiza-tion. (Hypertension. 1998;32:831-837.) Key Words: hypertrophy, cardiac n G proteins n adenylyl cyclase n catecholamines In the failing myocardium, an activation of the tissuerenin-angiotensin system (RAS) occurs. In addition, sym-pathetic stimulation1 produces a decrease of cardiac b-adrenoceptors2,3 and increased expression of inhibitory G-protein a-subunits (Gia),3–5 resulting in a desensitization o