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

Abstract

In human heart failure, desensitization of the β-adrenergic signal transduction has been reported to be one of the main pathophysiological alterations. However, data on the β-adrenergic system in human compensated cardiac hypertrophy are very limited. Therefore, we studied the myocardial β-adrenergic signaling in patients suffering from hypertrophic obstructive cardiomyopathy (HOCM, n = 9) or from aortic valve stenosis (AoSt, n = 8). β-Adrenoceptor density determined by [125I]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 α-subunit (Gsα) measured by immunoblotting was unchanged, whereas the inhibitory G protein α-subunit (Gαi-2) was increased. In contrast, in AoSt, Gαi-2 protein was unchanged, but Gsα 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 β-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.