Recent Insights on Circulating Catecholamines in Hypertension

Abstract

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.

Deciphering the Mechanism of the Anti-Hypertensive Effect of Isorhynchophylline by Targeting Neurotransmitters Metabolism of Hypothalamus in Spontaneously Hypertensive Rats

“…Our study found that tyrosine content was significantly lower in SHRs than in WKYs and that catecholamines including dopamine, epinephrine, and homovanillic acid contents were obviously increased in the model group, consistent with findings in previous reports, confirming the role of catecholamines in the progression of hypertension. , Sympathetic activity is a key responder to regulate the blood pressure via secreting catecholamines . Isorhynchophylline reversed the increased epinephrine and NE contents that regulate vascular tone by activating α- and β-adrenergic receptors . Blocking α1-adrenergic receptor signaling in smooth muscle cells and inhibiting β-adrenergic receptor-mediated release of renin promoted vasodilatation and lower blood pressure .…”

“…Isorhynchophylline reversed the increased epinephrine and NE contents that regulate vascular tone by activating α- and β-adrenergic receptors . Blocking α1-adrenergic receptor signaling in smooth muscle cells and inhibiting β-adrenergic receptor-mediated release of renin promoted vasodilatation and lower blood pressure . These results indicated that isorhynchophylline might regulate blood pressure by modulating catecholamine synthesis in the hypothalamus.…”

Transcriptomic profiles reveal differences between the right and left ventricle in normoxia and hypoxia

“…Hypoxia mediates both cell autonomous and systemic changes, including endothelial signaling in the vasculature, which causes vasoconstriction in the systemic circulation but vasodilation in the pulmonary circulation. Shared genes altered in both ventricles during hypoxia may also result in the release of systemic factors such as circulating catecholamines (Ton & Hammes, ) that may cause similar responses via the shared coronary perfusion of both ventricles. Rat models of hypoxia exposure have been well‐characterized for physiological changes, and some studies have measured expression of key genes.…”

A systematic review of chromogranin A (CgA) and its biomedical applications, unveiling its structure-related functions

“…In contrast, the injection of CST decreased the catecholamine level in the plasma and contributed to lower blood pressure [5]. Therefore, a malfunction of the negative feedback system correlates highly with the development of essential hypertension [130].…”