[Adrenergic beta receptors and guanine nucleotide binding proteins (G-proteins) of the failing human heart].
In heart failure, the sympathetic nervous system is activated. The increased release of norepinephrine from the heart and the elevated levels of circulating catecholamines produce a downregulation of myocardial beta 1-adrenoceptors. In ischemic cardiomyopathy and mitral valve disease, a downregulation of beta 2-adrenoceptors has been observed also. The beta-adrenoceptor downregulation closely correlates to the reduced positive inotropic effects of beta-adrenoceptor agonists. In addition, an increase of the inhibitory guanine-nucleotide binding protein (Gi alpha) has been observed, while the levels of the stimulatory guanine-nucleotide binding protein (Gs alpha), the activity of the catalyst and the anti-adrenergic effects of A1-adenosine receptor- or m-cholinoceptor stimulation remain unchanged in the failing human heart. The increase of Gi alpha correlated closely to the reduced positive inotropic responses to the cAMP-phosphodiesterase inhibitor milrinone. In the failing human heart, the beta-adrenoceptor downregulation and the increased expression of Gi alpha represent pathobiochemical alterations which are involved in the reduced effects of cAMP-dependent positive inotropic agents. The therapeutic reversal of these pathobiochemical alterations is a future promise in the treatment of heart failure.
Böhm
M
M
Medizinische Klinik I, Universität München.
Schwinger
R H
RH
Erdmann
E
E
D019204:GTP-Binding Proteins / Q000502:physiology*; D006321:Heart / Q000294:innervation; D006333:Heart Failure / Q000503:physiopathology*; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D009200:Myocardial Contraction / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000503:physiopathology
D011943:Receptors, Adrenergic, beta; D019204:GTP-Binding Proteins
Beta-Adrenozeptoren und Guanin-Nukleotid-bindende Proteine (G-Proteine) am insuffizienten menschlichen Herzen.