Adrenal GRK2 lowering is an underlying mechanism for the beneficial sympathetic effects of exercise training in heart failure

作者：Rengo Giuseppe^*; Leosco Dario; Zincarelli Carmela; Marchese Massimo; Corbi Graziamaria; Liccardo Daniela; Filippelli Amelia; Ferrara Nicola; Lisanti Michael P; Koch Walter J; Lymperopoulos Anastasios

来源：American Journal of Physiology - Heart and Circulatory Physiology, 2010, 298(6): H2032-H2038.

DOI：10.1152/ajpheart.00702.2009

• sympathetic overactivity
• adrenal G protein-coupled receptor kinase-2
• catecholamines

Rengo G, Leosco D, Zincarelli C, Marchese M, Corbi G, Liccardo D, Filippelli A, Ferrara N, Lisanti MP, Koch WJ, Lymperopoulos A. Adrenal GRK2 lowering is an underlying mechanism for the beneficial sympathetic effects of exercise training in heart failure. Am J Physiol Heart Circ Physiol 298: H2032-H2038, 2010. First published March 19, 2010; doi:10.1152/ajpheart.00702.2009.-Exercise training has been reported to exert beneficial effects on cardiac function and to reduce morbidity and mortality of chronic heart failure (HF). Augmented sympathetic nervous system (SNS) activity, leading to elevated circulating catecholamine (CA) levels, is a hallmark of chronic HF that significantly aggravates this disease. Exercise training has been shown to also reduce SNS overactivity in HF, but the underlying molecular mechanism(s) remain unidentified. We recently reported that adrenal G protein-coupled receptor kinase-2 (GRK2), an enzyme that regulates the sympathoinhibitory alpha(2)-adrenoceptors (alpha(2)-ARs) present in the CA-producing adrenal medulla, is upregulated in HF, contributing to the chronically elevated CA levels and SNS activity of the disease. In the present study, we tested whether exercise training can affect the adrenal GRK2-alpha(2)-AR-CA production system in the context of HF. For this purpose, a 10-wk-long exercise training regimen of adult male Sprague-Dawley rats starting at 4 wk postmyocardial infarction (post-MI) was employed, and examination at the end of this treatment period revealed significant amelioration of beta-AR-stimulated contractility in response to exercise training, accompanied by cardiac GRK2 reduction and restoration of circulating plasma CA levels. Importantly, adrenal GRK2 expression (72 +/- 5% reduction vs. post-MI untrained) and alpha(2)-AR number were also restored after exercise training in post-MI animals. These results suggest that exercise training restores the adrenal GRK2-alpha(2)-AR-CA production axis, and this might be part of the mechanism whereby this therapeutic modality normalizes sympathetic overdrive and impedes worsening of the failing heart.

• 出版日期2010-6
• 单位东南大学