Nitric oxide and superoxide transport in a cross section of the rat outer medulla. II. Reciprocal interactions and tubulovascular cross talk.


Journal Article

In a companion study (Edwards A and Layton AT. Am J Physiol Renal Physiol. doi:10.1152/ajprenal.00680.2009), we developed a mathematical model of nitric oxide (NO), superoxide (O(2)(-)), and total peroxynitrite (ONOO) transport in mid-outer stripe and mid-inner stripe cross sections of the rat outer medulla (OM). We examined how the three-dimensional architecture of the rat OM, together with low medullary oxygen tension (Po(2)), affects the distribution of NO, O(2)(-), and ONOO in the rat OM. In the current study, we sought to determine generation rate and permeability values that are compatible with measurements of medullary NO concentrations and to assess the importance of tubulovascular cross talk and NO-O(2)(-) interactions under physiological conditions. Our results suggest that the main determinants of NO concentrations in the rat OM are the rate of vascular and tubular NO synthesis under hypoxic conditions, and the red blood cell (RBC) permeability to NO (P(NO)(RBC)). The lower the P(NO)(RBC), the lower the amount of NO that is scavenged by hemoglobin species, and the higher the extra-erythrocyte NO concentrations. In addition, our results indicate that basal endothelial NO production acts to significantly limit NaCl reabsorption across medullary thick ascending limbs and to sustain medullary perfusion, whereas basal epithelial NO production has a smaller impact on NaCl transport and a negligible effect on vascular tone. Our model also predicts that O(2)(-) consumption by NO significantly reduces medullary O(2)(-) concentrations, but that O(2)(-) , when present at subnanomolar concentrations, has a small impact on medullary NO bioavailability.

Full Text

Duke Authors

Cited Authors

  • Edwards, A; Layton, AT

Published Date

  • September 2010

Published In

Volume / Issue

  • 299 / 3

Start / End Page

  • F634 - F647

PubMed ID

  • 20519375

Pubmed Central ID

  • 20519375

Electronic International Standard Serial Number (EISSN)

  • 1522-1466

International Standard Serial Number (ISSN)

  • 1931-857X

Digital Object Identifier (DOI)

  • 10.1152/ajprenal.00681.2009


  • eng