Targeting the Renin-Angiotensin-Aldosterone System to Prevent Hypertension and Kidney Disease of Developmental Origins

Int J Mol Sci. 2021 Feb 25;22(5):2298. doi: 10.3390/ijms22052298.

Abstract

The renin-angiotensin-aldosterone system (RAAS) is implicated in hypertension and kidney disease. The developing kidney can be programmed by various early-life insults by so-called renal programming, resulting in hypertension and kidney disease in adulthood. This theory is known as developmental origins of health and disease (DOHaD). Conversely, early RAAS-based interventions could reverse program processes to prevent a disease from occurring by so-called reprogramming. In the current review, we mainly summarize (1) the current knowledge on the RAAS implicated in renal programming; (2) current evidence supporting the connections between the aberrant RAAS and other mechanisms behind renal programming, such as oxidative stress, nitric oxide deficiency, epigenetic regulation, and gut microbiota dysbiosis; and (3) an overview of how RAAS-based reprogramming interventions may prevent hypertension and kidney disease of developmental origins. To accelerate the transition of RAAS-based interventions for prevention of hypertension and kidney disease, an extended comprehension of the RAAS implicated in renal programming is needed, as well as a greater focus on further clinical translation.

Keywords: angiotensin-converting enzyme; chronic kidney disease; developmental origins of health and disease (DOHaD); hypertension; nephron; nitric oxide; oxidative stress; renin-angiotensin-aldosterone system.

Publication types

  • Review

MeSH terms

  • Adult
  • Animals
  • Disease Models, Animal
  • Dysbiosis / metabolism
  • Epigenesis, Genetic
  • Humans
  • Hypertension / genetics
  • Hypertension / metabolism*
  • Kidney / growth & development*
  • Kidney / metabolism
  • Kidney Diseases / enzymology
  • Kidney Diseases / genetics
  • Kidney Diseases / metabolism*
  • Nephrons / cytology
  • Nephrons / growth & development*
  • Nephrons / metabolism
  • Nitric Oxide / deficiency
  • Nitric Oxide / metabolism
  • Oxidative Stress / genetics
  • Oxidative Stress / physiology
  • Renin / metabolism*
  • Renin-Angiotensin System* / genetics
  • Renin-Angiotensin System* / physiology

Substances

  • Nitric Oxide
  • Renin