Changes of beta-adrenergic signaling in compensated human cardiac hypertrophy depend on the underlying disease

In human heart failure, desensitization of the beta-adrenergic signal transduction has been reported to be one of the main pathophysiological alterations. However, data on the beta-adrenergic system in human compensated cardiac hypertrophy are very limited. Therefore, we studied the myocardial beta-...

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Bibliographic Details
Published in:	American journal of physiology. Heart and circulatory physiology Vol. 278; no. 6; p. H2076
Main Authors:	Schotten, U, Filzmaier, K, Borghardt, B, Kulka, S, Schoendube, F, Schumacher, C, Hanrath, P
Format:	Journal Article
Language:	English
Published:	United States 01-06-2000
Subjects:	Adaptation, Physiological Adenylyl Cyclases - metabolism Adult Aortic Valve Stenosis - metabolism Cardiomegaly - etiology Cardiomegaly - physiopathology Female GTP-Binding Proteins - metabolism Humans Male Middle Aged Myocardium - metabolism Receptors, Adrenergic, beta - metabolism Receptors, Adrenergic, beta - physiology Signal Transduction - physiology Ventricular Dysfunction, Left
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Summary:	In human heart failure, desensitization of the beta-adrenergic signal transduction has been reported to be one of the main pathophysiological alterations. However, data on the beta-adrenergic system in human compensated cardiac hypertrophy are very limited. Therefore, we studied the myocardial beta-adrenergic signaling in patients suffering from hypertrophic obstructive cardiomyopathy (HOCM, n = 9) or from aortic valve stenosis (AoSt, n = 8). beta-Adrenoceptor density determined by [(125)I]iodocyanopindolol binding was reduced in HOCM and AoSt compared with nonhypertrophied, nonfailing myocardium (NF) of seven organ donors. In HOCM the protein expression of stimulatory G protein alpha-subunit (G(s)alpha) measured by immunoblotting was unchanged, whereas the inhibitory G protein alpha-subunit (Galpha(i-2)) was increased. In contrast, in AoSt, Galpha(i-2) protein was unchanged, but G(s)alpha protein was increased. Adenylyl cyclase stimulation by isoproterenol was reduced in HOCM but not in AoSt. Plasma catecholamine levels were normal in all patients. In conclusion, both forms of hypertrophy are associated with beta-adrenoceptor downregulation but with different changes at the G protein level that occur before symptomatic heart failure due to progressive dilatation of the left ventricle develops and are not due to elevated plasma catecholamine levels.
ISSN:	0363-6135
DOI:	10.1152/ajpheart.2000.278.6.H2076