Oxidant-redox regulation of pulmonary vascular responses to hypoxia and nitric oxide-cGMP signaling

Cardiol Rev. 2010 Mar-Apr;18(2):89-93. doi: 10.1097/CRD.0b013e3181c9f088.


Most current theories for the mechanism of hypoxic pulmonary vasoconstriction (HPV) include a role for reactive oxygen species and/or changes in redox regulation, but extreme controversy exists regarding which systems and redox changes mediate the HPV response. Nitric oxide (NO) appears to help to maintain low pulmonary arterial pressure, suppress HPV, and prevent the development of pulmonary hypertension. Our studies have found a key role for glucose-6-phosphate dehydrogenase in bovine pulmonary arterial smooth muscle functioning to maintain elevated levels of cytosolic NADPH which fuels the generation of vasodilator levels of hydrogen peroxide. HPV results from hypoxia removing vasodilation by peroxide. Decreased superoxide generation by Nox4 oxidase and its conversion to peroxide by Cu,Zn-SOD appear to be potential factors in sensing hypoxia, and decreased cGMP-associated vasodilation and removal of redox controlled vasodilator mechanisms by increased cytosolic NADPH may be key coordinators of the HPV response. Oxidant generation associated with vascular disease processes, including the removal of NO by superoxide, and attenuation of its ability to stimulate cGMP production by oxidation of the heme and thiols of soluble guanylate cyclase attenuate potential beneficial actions of NO on pulmonary arterial function. While pulmonary hypertension appears to have multiple poorly understood effects on redox-associated processes, potentially influencing responses to hypoxia and NO-cGMP signaling, much remains to be elucidated regarding how these processes may be important factors in the progression, expression and therapeutic treatment of pulmonary hypertension.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cyclic GMP / metabolism*
  • Cytosol
  • Disease Progression
  • Glucosephosphate Dehydrogenase / metabolism
  • Humans
  • Hydrogen Peroxide / metabolism
  • Hypertension, Pulmonary / physiopathology*
  • Hypoxia / complications
  • Hypoxia / physiopathology*
  • NADP / metabolism
  • Nitric Oxide / metabolism*
  • Oxidants / metabolism
  • Oxidation-Reduction
  • Pulmonary Artery / physiology*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Vasoconstriction / physiology
  • Vasodilation / physiology


  • Oxidants
  • Reactive Oxygen Species
  • Nitric Oxide
  • NADP
  • Hydrogen Peroxide
  • Glucosephosphate Dehydrogenase
  • Cyclic GMP