[Alterations in sympathoadrenal system in congestive heart failure].
Although sympathoadrenal system has a pivotal role in maintaining homeostasis during stress, protracted activation adversely affects life expectancy in patients with heart failure. Detrimental effects of sympathoadrenal activation over time have been confirmed using transgenic mice overexpressing beta 1-adrenergic receptors, which showed that initial hypercontractility led to cardiac hypertrophy with failure, resulting in premature death. Mechanisms underlying such adverse effects involve multiple biological events including production of oxygen free radicals, cytokines, matrix metalloproteinase, apoptosis, cardiac hypertrophy, and chamber remodeling as well as energy expenditure. Desensitization phenomenon of the beta-adrenergic receptors is one of the predominant features characterizing congestive heart failure. Down-regulation of the receptors, increases in inhibitory guanine-nucleotide(G) protein and G-protein-coupled receptor kinases are responsible for the phenomenon.
Yoshikawa
Tsutomu
T
Cardiopulmonary Division, Department of Medicine, Keio University School of Medicine.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015551:Autoimmunity; D015536:Down-Regulation; D019204:GTP-Binding Proteins / Q000378:metabolism; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D020257:Ventricular Remodeling
D011943:Receptors, Adrenergic, beta; D019837:Ryanodine Receptor Calcium Release Channel; D017346:Protein Serine-Threonine Kinases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases