Oxidative stress and nitric oxide deficiency in the kidney: a critical link to hypertension?

Am J Physiol Regul Integr Comp Physiol. 2005 Oct;289(4):R913-35. doi: 10.1152/ajpregu.00250.2005.


There is growing evidence that oxidative stress contributes to hypertension. Oxidative stress can precede the development of hypertension. In almost all models of hypertension, there is oxidative stress that, if corrected, lowers BP, whereas creation of oxidative stress in normal animals can cause hypertension. There is overexpression of the p22(phox) and Nox-1 components of NADPH oxidase and reduced expression of extracellular superoxide dismutase (EC-SOD) in the kidneys of ANG II-infused rodents, whereas there is overexpression of p47(phox) and gp91(phox) and reduced expression of intracellular SOD with salt loading. Several mechanisms have been identified that can make oxidative stress self-sustaining. Reactive oxygen species (ROS) can enhance afferent arteriolar tone and reactivity both indirectly via potentiation of tubuloglomerular feedback and directly by microvascular mechanisms that diminish endothelium-derived relaxation factor/nitric oxide responses, generate a cyclooxygenase-2-dependent endothelial-derived contracting factor that activates thromboxane-prostanoid receptors, and enhance vascular smooth muscle cells reactivity. ROS can diminish the efficiency with which the kidney uses O(2) for Na(+) transport and thereby diminish the P(O(2)) within the kidney cortex. This may place a break on further ROS generation yet could further enhance vasculopathy and hypertension. There is a tight relationship between oxidative stress in the kidney and the development and maintenance of hypertension.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Disease Susceptibility / metabolism
  • Humans
  • Hypertension / etiology
  • Hypertension / metabolism*
  • Kidney / metabolism*
  • Models, Biological*
  • Nitric Oxide / deficiency*
  • Nitric Oxide Synthase / metabolism
  • Oxidative Stress*
  • Reactive Oxygen Species / metabolism*
  • Water-Electrolyte Imbalance / complications
  • Water-Electrolyte Imbalance / metabolism*


  • Reactive Oxygen Species
  • Nitric Oxide
  • Nitric Oxide Synthase