The role of reactive oxygen species in the regulation of tubular function

The phrase reactive oxygen species covers a number of molecules and atoms, including the quintessential member of the group, O2-; singlet oxygen; H2O2; organic peroxides; and OONO-. While nitric oxide (NO) is also technically a member of the reactive oxygen species family, it is generally considered with a different class of compounds and will not be considered here. To our knowledge, there are currently no published data reporting the effects of reactive oxygen species on net transepithelial flux in the proximal nephron. However, there is evidence that OONO- regulates Na+/K+ adenosine triphosphatase (ATPase) activity as well as paracellular permeability. While it is easy to speculate that such an effect on the pump would decrease net transepithelial solute and water reabsorption, one cannot do so without knowing how other transporters are affected. O2- stimulates NaCl absorption by the thick ascending limb by activating protein kinase C and blunting the effects of NO. The effects of O2- on thick ascending limb NaCl absorption may be important for the initiation of salt-sensitive hypertension. To our knowledge, there are no published data concerning the role of reactive oxygen species in the regulation of solute absorption in either the distal convoluted tubule or the collecting duct. However, OONO- inhibits basolateral K+ channels in the cortical collecting duct, although the net effect of such inhibition is unknown.

While the regulation of tubular transport by reactive oxygen species is important to overall salt and water balance, we know very little about where and how these regulators act along the nephron.