Recent insights on circulating catecholamines in hypertension

Pheochromocytomas are neuroendocrine tumors that commonly lead to excess catecholamine secretion, resulting in elevated blood pressure. In addition to potentiating vasoconstriction, catecholamines promote endothelial dysfunction, as evidenced by elevated markers of endothelial dysfunction, ADMA and sVCAM-1, in patients with pheochromcytoma. Importantly, catecholamine-induced endothelial dysfunction and hypertension may not only be due to catecholamine production by neuroendocrine tumors, as vascular endothelial cells have now been demonstrated to synthesize and secrete catecholamines. This local vascular catecholamine release appears to be triggered by hypoxia. In fact, chronic intermittent hypoxia both in vitro and in vivo leads to stabilization of hypoxic-inducible factors that increase gene expression of catecholamine-synthesizing enzymes. In an effort to target catecholamines as a means of treating hypertension, novel therapeutic options are being explored, including the generation of pharmacophores that mimic the suppressive effects of catestatin on catecholamine release as well as the use of renalase enhancers to increase catecholamine metabolism.