Contribution of mitochondrial oxidative stress to hypertension

Curr Opin Nephrol Hypertens. 2016 Mar;25(2):73-80. doi: 10.1097/MNH.0000000000000198.

Abstract

Purpose of review: In 1954 Harman proposed the free radical theory of aging, and in 1972 he suggested that mitochondria are both the source and the victim of toxic free radicals. Interestingly, hypertension is an age-associated disease and clinical data show that by age 70, 70% of the population has hypertension and this is accompanied by oxidative stress. Antioxidant therapy, however, is not currently available and common antioxidants such as ascorbate and vitamin E are ineffective in preventing hypertension. The present review focuses on the molecular mechanisms of mitochondrial oxidative stress and the therapeutic potential of targeting mitochondria in hypertension.

Recent findings: Over the past several years, we have shown that the mitochondria become dysfunctional in hypertension and have defined a novel role of mitochondrial superoxide radicals in this disease. We have shown that genetic manipulation of mitochondrial antioxidant enzyme superoxide dismutase affects blood pressure, and have developed mitochondria-targeted therapies such as mitochondrial superoxide dismutase mimetics that effectively lower blood pressure. However, the specific mechanism of mitochondrial oxidative stress in hypertension remains unclear. Recent animal and clinical studies have demonstrated several hormonal, metabolic, inflammatory, and environmental pathways contributing to mitochondrial dysfunction and oxidative stress.

Summary: Nutritional supplements, calorie restriction, and life style change are the most effective preventive strategies to improve mitochondrial function and reduce mitochondrial oxidative stress. Aging associated mitochondrial dysfunction, however, reduces the efficacy of these strategies. Therefore, we propose that new classes of mitochondria-targeted antioxidants can provide a high therapeutic potential to improve endothelial function and reduce hypertension.

Publication types

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

MeSH terms

  • Aging / metabolism*
  • Angiotensin II / metabolism
  • Animals
  • Caloric Restriction
  • Humans
  • Hypertension / drug therapy
  • Hypertension / metabolism*
  • Mitochondria / metabolism*
  • Motor Activity
  • Oxidative Stress*
  • Reactive Oxygen Species / metabolism*
  • Sirtuin 3 / metabolism
  • Smoking
  • Superoxide Dismutase / metabolism

Substances

  • Reactive Oxygen Species
  • Angiotensin II
  • Superoxide Dismutase
  • Sirtuin 3