The interplay between Angiotensin II, TLR4 and hypertension

Pharmacol Res. 2017 Jun:120:88-96. doi: 10.1016/j.phrs.2017.03.017. Epub 2017 Mar 19.

Abstract

Hypertension is a multifactorial disease. Although a number of different underlying mechanisms have been learned from the various experimental models of the disease, hypertension still poses challenges for treatment. Angiotensin II plays an unquestionable role in blood pressure regulation acting through central and peripheral mechanisms. During hypertension, dysregulation of the Renin-Angiotensin System is associated with increased expression of pro-inflammatory cytokines and reactive oxygen species causing kidney damage, endothelial dysfunction, and increase in sympathetic activity, among other damages, eventually leading to decline in organ function. Recent studies have shown that these effects involve both the innate and the adaptive immune response. The contribution of adaptive immune responses involving different lymphocyte populations in various models of hypertension has been extensively studied. However, the involvement of the innate immunity mediating inflammation in hypertension is still not well understood. The innate and adaptive immune systems intimately interact with one another and are essential to an effectively functioning of the immune response; hence, the importance of a better understanding of the underlying mechanisms mediating innate immune system during hypertension. In this review, we aim to discuss mechanisms linking Angiotensin II and the innate immune system, in the pathogenesis of hypertension. The newest research investigating Angiotensin II triggering toll like receptor 4 activation in the kidney, vasculature and central nervous system contributing to hypertension will be discussed. Understanding the role of the innate immune system in the development of hypertension may bring to light new insights necessary to improve hypertension management.

Keywords: Angiotensin II; Central nervous system; Hypertension; Innate immune system; Kidney; Vasculature.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity
  • Angiotensin II / immunology*
  • Animals
  • Brain / immunology
  • Brain / pathology
  • Humans
  • Hypertension / complications
  • Hypertension / immunology*
  • Hypertension / pathology
  • Immunity, Innate
  • Inflammation / complications
  • Inflammation / immunology
  • Inflammation / pathology
  • Kidney / immunology
  • Kidney / pathology
  • Renin-Angiotensin System
  • Signal Transduction
  • Toll-Like Receptor 4 / immunology*

Substances

  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Angiotensin II