Pflügers Archiv - European Journal of Physiology

, Volume 459, Issue 2, pp 325–332

Angiotensin receptors as determinants of life span

  • Paola Cassis
  • Sara Conti
  • Giuseppe Remuzzi
  • Ariela Benigni
Integrative Physiology

DOI: 10.1007/s00424-009-0725-4

Cite this article as:
Cassis, P., Conti, S., Remuzzi, G. et al. Pflugers Arch - Eur J Physiol (2010) 459: 325. doi:10.1007/s00424-009-0725-4

Abstract

Angiotensin II (Ang II), the central product of renin-angiotensin system, has a role in the etiology of hypertension and in pathophysiology of cardiac and renal diseases in humans. Other functions of Ang II include effects on immune response, inflammation, cell growth and proliferation, which are largely mediated by Ang II type 1 receptor (AT1). Several experimental studies have demonstrated that Ang II acts through AT1 as a mediator of normal aging processes by increasing oxidant damage to mitochondria and in consequences by affecting mitochondrial function. Recently, our group has demonstrated that the inhibition of Ang II activity by targeted disruption of the Agtr1a gene encoding Ang II type 1A receptor (AT1A) in mice translates into marked prolongation of life span. The absence of AT1A protected multiple organs from oxidative damage and the alleviation of aging-like phenotype was associated with increased number of mitochondria and upregulation of the prosurvival gene sirtuin 3. AT1 receptor antagonists have been proven safe and well-tolerated for chronic use and are used as a key component of the modern therapy for hypertension and cardiac failure, therefore Ang II/AT1 pathway represents a feasible therapeutic strategy to prolong life span in humans.

Keywords

Oxidative stressMitochondriaAgingAngiotensinInflammation

Abbreviation

RAS

renin-angiotensin system

Ang II

angiotensin II

ACE

angiotensin converting enzyme

AT1

Ang II type 1 receptor

AT2

Ang II type 2 receptor

NO

nitric oxide

eNOS

endothelial nitric oxide synthase

ROS

reactive oxygen species

ACEi

angiotensin-converting enzyme inhibitors

ARBs

angiotensin II receptor blockers

SIRT

sirtuin

Nampt

nicotinamide phosphoribosyltransferase

IGF-1

insulin growth factor-1

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Paola Cassis
    • 1
  • Sara Conti
    • 1
  • Giuseppe Remuzzi
    • 1
    • 2
  • Ariela Benigni
    • 1
  1. 1.Mario Negri Institute for Pharmacological ResearchBergamoItaly
  2. 2.Unit of Nephrology and Dialysis, Azienda OspedalieraOspedali Riuniti di BergamoBergamoItaly