Stress-dependent hypertension and the role of T lymphocytes

Abstract

Hypertension is a significant global health burden that is associated with an increased risk of stroke, atherosclerosis and other cardiovascular diseases. Several risk factors, including high dietary salt, obesity, genetics and race, as well as behavioural and psychological factors, contribute to development of this complex disease. Various hypertensive stimuli enhance sympathetic drive and promote autonomic dysfunction leading to elevated blood pressure. As our understanding of the pathogenesis and end-organ damage associated with hypertension increases, mounting evidence also highlights the role of inflammation in this process and, in particular, the role of the adaptive immune system and T cells. This review discusses recent findings regarding the role of the central nervous system, T lymphocytes and the impact of cardiovascular risk factors, such as psychological stress, in hypertension.

Figure 1

Schematic showing location and connections of some of the primary hypothalamic structures responsible for central angiotensin II signaling and the integration of the stress response. SFO, Subfornical organ; BNST, Bed nucleus stria terminalis; MPO, Median preoptic nucleus; PVN, paraventricular nucleus; CeA, Central amygdala; NTS, the nucleus of the solitary tract; RVLM, rostral ventrolateral medulla; PBN, parabrachial nucleus; AP, area postrema.

Figure 2

We propose that hypertensive stimuli such as angiotensin II, salt and chronic stress act on the CNS to increase sympathetic outflow in part via the circumventricular organs. Increased sympathetic outflow to the kidneys and vasculature leads to a modest elevation in blood pressure, which promotes the formation of unknown antigens that are processed by antigen presenting cells, leading to T cell activation. Direct autonomic innervation of lymphoid tissue and immune cells may also contribute to this pathway. Activated T cells infiltrate the vasculature and kidney, interacting with monocyte/macrophages and promote pro-inflammatory cytokine release, endothelial dysfunction, further vasoconstriction, salt /water retention and ultimately severe hypertension.