Role of adrenal GRK2 in heart failure

Heart failure (HF) is characterized by sympathetic hyperactivity and enhanced circulating catecholamines (CA's). CA's stimulating cardiac function are norepinephrine released from cardiac sympathetic nerves and circulating CA's secreted from the adrenal gland. Adrenal α2-adrenoceptors (α2ARs), which are regulated by G-protein coupled receptor kinase-2 (GRK2), exert autocrine feedback inhibition on CA secretion. We sought to investigate whether adrenal GRK2 activity is abnormal in HF, leading to enhanced CA secretion. For this purpose, we used the rat model of chronic HF due to myocardial infarction. In this model, adrenal GRK2 mRNA and protein were found up-regulated, and this correlated with severe desensitization of adrenal α2ARs. Thus, in HF, adrenal GRK2 up-regulation increases CA secretion, thus contributing to the sympathetic overstimulation of the failing heart.