Cardiac sympathetic nerve terminal function in congestive heart failure.
Increased cardiac release of norepinephrine (NE) and depleted cardiac stores of NE are two salient features of the human failing heart. Researches from my laboratory have shown that these changes are accompanied by a functional defect of NE uptake in the cardiac sympathetic nerve terminals. Our studies have shown that the decrease of NE uptake is caused by reduction of NE transporter density in the sympathetic nerve endings, and this change is responsible, at least in part, for the increased myocardial interstitial NE, decreased myocardial adrenoceptor density, and increased myocyte apoptosis in experimental cardiomyopathies. We have also provided evidence in both intact animals and cultured PC12 cells that the decrease of NE transporter is induced by the actions of oxidative metabolites of exogenous NE, involving endoplasmic reticulum stress and impaired N-glycosylation of the NE transporter. This change in the cardiac sympathetic NE uptake function, as demonstrated by [123I] metaiodobenzylguanidine in human studies, may not only serve as an important prognostic variable in patients with congestive heart failure, but also be used as a surrogate for the efficacies of various therapeutic interventions for heart failure. Finally, increasing evidence suggests and further studies are needed to show that the cardiac sympathetic nerve terminal function may be a direct target for pharmacologic treatment of congestive heart failure.
Liang
Chang-seng
CS
School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA. chang-seng_liang@urmc.rochester.edu
D019797:3-Iodobenzylguanidine; D006321:Heart / Q000294:innervation* / Q000502:physiology; D006333:Heart Failure / Q000175:diagnosis / Q000503:physiopathology*; D006801:Humans; D009638:Norepinephrine / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D019275:Radiopharmaceuticals; D013564:Sympathetic Nervous System / Q000502:physiology*
D050484:Norepinephrine Plasma Membrane Transport Proteins; D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine; D009638:Norepinephrine