The importance of bone marrow and the immune system in driving increases in blood pressure and sympathetic nerve activity in hypertension.

NEW FINDINGS What is the topic of this review? This manuscript provides a review of the current understanding of the role of the sympathetic nervous system in regulation of the bone marrow-derived immune cells and their involvement in hypertension. What advances does it highlight? We highlight the recent advances in understanding of the neuro-immune interactions both peripherally and centrally as they relate to blood pressure control. ABSTRACT The sympathetic nervous system (SNS) plays a crucial role in maintaining physiological homeostasis in part by regulating, integrating, and orchestrating processes between many physiological systems, including the immune system (Abboud, Harwani, & Chapleau, 2012; Kenney & Ganta, 2014; Pongratz & Straub, 2014). Sympathetic nerves innervate all primary and secondary immune organs (Pongratz & Straub, 2014), and all cells of the immune system express beta-adrenoreceptors (Baker & Fuller, 1995; Gurguis, Vo, Griffith, & Rush, 1999; Manni, Granstein, & Maestroni, 2011). In turn, immune cells can produce cytokines, chemokines, and neurotransmitters capable of modulating neuronal activity and ultimately SNS activity (Chavan, Pavlov, & Tracey, 2017; Kerage, Sloan, Mattarollo, & McCombe, 2019; R. J. Miller, Jung, Bhangoo, & White, 2009). Thus, the essential role of the SNS in regulation of innate and adaptive immune functions is mediated in part via beta-adrenoreceptor activation of bone marrow cells by, norepinephrine. Interestingly, both central and systemic inflammation are well-established hallmarks of hypertension (HTN) and its comorbidities (De Miguel, Rudemiller, Abais, & Mattson, 2015; Haspula & Clark, 2018; A. A. Miller & Spencer, 2014; Telle-Hansen, Christensen, Ulven, & Holven, 2017), including an inflammatory process involving the transmigration and infiltration of immune cells into tissues. We propose that physiological states which prolong beta-adrenoreceptor activation in bone marrow can disrupt neuroimmune homeostasis and impair communication between the immune system and SNS, leading to immune dysregulation, which in turn is sustained via a central mechanism involving neuroinflammation.The Sympathetic Nervous System is Dysregulated in Hypertension This article is protected by copyright. All rights reserved.