Dysfunctional Brain-bone Marrow Communication: A Paradigm Shift in the Pathophysiology of Hypertension

Abstract

It is widely accepted that the pathophysiology of hypertension involves autonomic nervous system dysfunction, as well as a multitude of immune responses. However, the close interplay of these systems in the development and establishment of high blood pressure and its associated pathophysiology remains elusive and is the subject of extensive investigation. It has been proposed that an imbalance of the neuro-immune systems is a result of an enhancement of the “pro-inflammatory sympathetic” arm in conjunction with dampening of the “anti-inflammatory parasympathetic” arm of the autonomic nervous system. In addition to the neuronal modulation of the immune system, it is proposed that key inflammatory responses are relayed back to the central nervous system and alter the neuronal communication to the periphery. The overall objective of this review is to critically discuss recent advances in the understanding of autonomic immune modulation, and propose a unifying hypothesis underlying the mechanisms leading to the development and maintenance of hypertension, with particular emphasis on the bone marrow, as it is a crucial meeting point for neural, immune, and vascular networks.

Importance of Inflammation in Hypertension - Review

“…O NO e as ERO são componentes da resposta imune inata, e são produzidos por macrófagos modulando a atividade, função e sobrevivência de linfócitos T, linfócitos B e células dendríticas. (HARRISON et al, 2011;SCHIFFRIN, 2013;SANTISTEBAN et al, 2013).…”

“…Entretanto, quando administrada pela via intravenosa a angiotensina II pode estar relacionada com a HAS, lesão glomerular, proteinúria e fibrose intersticial no tecido renal (CAMPBELL, 2013). Ganta et al (2005) e Santisteban et al (2013) reportaram que a administração de angiotensina II, aumenta a atividade do SNS do baço, gânglios linfáticos e da medula óssea, que por sua vez aumenta a atividade e liberação de linfócitos T circulantes e mediadores inflamatórios como IL-1, IL-2, IL-6 e IL-16 na circulação, resultando em disfunção endotelial e inflamação vascular.…”

“…Desse modo, o efeito antiinflamatório parassimpático pode ser considerado como um potencial alvo terapêutico em indivíduos hipertensos (SANTISTEBAN et al 2013).…”

“…Os componentes do sistema renina angiotensina aldosterona (SRAA) funcionam como agentes pró-inflamatórios que participam da inflamação vascular (SAVOIA; SCHIFFRIN, 2006;HARRISON, 2013;SANTISTEBAN et al, 2013).…”

Relevance of Immune-Sympathetic Nervous System Interplay for the Development of Hypertension

“…It is widely accepted that the pathophysiology of hypertension includes autonomic nervous system dysfunction, as well as immune system involvement (Guzik et al 2007;Zubcevic et al 2011;de Kloet et al 2013;Santisteban et al 2013). However, the close relationship between these systems in the pathogenesis of hypertension and in particular the role of the brain in this interaction is still evolving.…”