Abstract
The immune system is increasingly recognized for its role in the genesis and progression of hypertension. The adrenal gland is a major site that coordinates the stress response via the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal system. Catecholamines released from the adrenal medulla function in the neuro-hormonal regulation of blood pressure and have a well-established link to hypertension. The immune system has an active role in the progression of hypertension and cytokines are powerful modulators of adrenal cell function. Adrenal medullary cells integrate neural, hormonal, and immune signals. Changes in adrenal cytokines during the progression of hypertension may promote blood pressure elevation by influencing catecholamine biosynthesis. This review highlights the potential interactions of cytokine signaling networks with those of catecholamine biosynthesis within the adrenal, and discusses the role of cytokines in the coordination of blood pressure regulation and the stress response.
Highlights
Hypertension—The Roles of Catecholamines and InflammationHypertension Approximately one in five Canadian adults live with hypertension; globally about 40% of adults over the age of 25 are hypertensive [1, 2]
This study identified the role of the cytokine TNF-α in blood pressure (BP) elevation when mice treated with Ang II responded with both increased BP and increased synthesis of TNF-α from T-cells; anti-TNF-α therapy with etanercept blunted Ang II-mediated elevations in BP [69]
As long as GRIP1 protein levels are sufficiently low in adrenal chromaffin cells, this competitive mechanism could allow for the converse effect, whereby induction of the STAT1-STAT2-IRF9 complex by IFN-α leads to an inhibition of glucocorticoid receptors (GRs) transcriptional effects through the repression of GRIP1 coactivation of GR
Summary
Hypertension—The Roles of Catecholamines and InflammationHypertension Approximately one in five Canadian adults live with hypertension; globally about 40% of adults over the age of 25 are hypertensive [1, 2]. These studies suggest the potential for enhanced neural activation of T-cells in hypertension as well as a functional importance of cytokine signaling in BP regulation. Studies in rat pheochromocytoma cells show that, in addition to PNMT, GCs regulate the other CA biosynthetic enzymes to produce parallel increases in their transcript level and activity [136, 138,139,140,141].
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