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Functional neural-bone marrow pathways: implications in hypertension and cardiovascular disease.

Treatment-resistant hypertension (TRHT) is characterized by persistently high arterial blood pressure (BP), partly as a result of a dysfunctional autonomic nervous system (ANS), wherein sympathetic drive/norepinephrine spillover is increased and parasympathetic drive is decreased.1–3 The difficulty in treatment of TRHT arises precisely from this partly neurogenic component because the available drug therapies do not target the central nervous system (CNS) directly. Because of this and despite recent advances in techniques such as renal denervation and carotid baroreceptor activation,4,5 successful treatment and long-term control of TRHT remain challenging.6 In an attempt to develop more effective treatments, many groups are investigating specific causes of TRHT. A large body of experimental evidence implicates both genetic and environmental influences, such as salt sensitivity and elevated systemic renin–angiotensin system (RAS) activity7–14 in the pathophysiology of this disease. Furthermore, a majority of studies point to dysregulations in the activity within the cardiorespiratory brain regions as a reason for increased sympathetic and decreased parasympathetic drive to the peripheral organs,14–21 resulting in end-organ damage,21–25 vascular/endothelial dysfunction,26,27 and hormonal imbalance,28 which perpetuate the pathophysiology and complicate treatment strategies. Despite our increasing understanding of TRHT, the origins of this brain dysregulation remain largely unknown. Recently, the activity of the immune system29–31 and neuroimmune pathways in patients with hypertension and animal models of hypertension has been highlighted.32–36 Studies suggest that both the sympathetic and the parasympathetic arms of the ANS can exert their influence on the activity of the immune organs, tissues, and cells, and that it is the dysfunctional ANS-immune communication that may lead to hypertension and CVD.35–40 The aim of this review is to summarize the latest advances in this …