The bidirectional interaction between the sympathetic nervous system and immune mechanisms in the pathogenesis of hypertension

Abstract

Over the last few years, evidence has accumulated to suggest that hypertension is, at least in part, an immune-mediated inflammatory disorder. Many links between immunity and hypertension have been established and provide a complex framework of mechanistic interactions contributing to the rise in BP. These include immune-mediated inflammatory processes affecting regulatory brain nuclei and interactions with other mediators of cardiovascular regulation such as the sympathetic nervous system. Sympathoexcitation differentially regulates T-cells based upon activation status of the immune cell as well as the resident organ. Exogenous and endogenous triggers activate signalling pathways in innate and adaptive immune cells resulting in pro-inflammatory cytokine production and activation of T-lymphocytes in the cardiovascular and renal regions, now considered major factors in the development of essential hypertension. The inflammatory cascade is sustained and exacerbated by the immune flow via the brain-bone marrow-spleen-gastrointestinal axis and thereby further aggravating immune-mediated pathways resulting in a vicious cycle of established hypertension and target organ damage. This review summarizes the evidence and recent advances in linking immune-mediated inflammation, sympathetic activation and their bidirectional interactions with the development of hypertension. LINKED ARTICLES: This article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc.

Conflict of interest statement

The authors declare no conflicts of interest.

© 2018 The British Pharmacological Society.

Figures

Figure 1

The ‘first hit pro‐inflammatory phase’ of pre‐ hypertension. Hypertensive (HTN) signals, damage‐associated molecular patterns (DAMPs) and cytokine‐dependent ROS signalling causes protein modification generating new neoantigens such as oxidized LDL, modified receptor proteins, HSPs and platelet glycoproteins that elicit an immunological response in the cardiovascular target tissues via the activation of T‐cells. This phase initiates the inflammatory cascade in organs associated with BP regulation. NAdr, noradrenaline.

Figure 2

The sympathetic–immune crosstalk results in established hypertension. The brain–BM–spleen–gastrointestinal (GI) axis perpetuates and further exaggerates the immune cascade by causing immune infiltration and immune‐mediated inflammatory damage in the organs regulating BP, ultimately resulting in established hypertension. MHC, major histocompatibility complex; TCR, T‐cell receptor.