Nitric oxide production by mouse renal tubules can be increased by a sodium-dependent mechanism

Stephen Kempson, Nathan Thompson, Laura Pezzuto, H. Glenn Bohlen

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Renal tubules process large amounts of NaCl that other investigators indicate increases tubular generation of nitric oxide. We questioned whether medullary or superficial cortical tubules would have the greater increase in nitric oxide concentration, [NO], when stressed by sodium and if the sodium/calcium exchanger was involved. Sodium stress in proximal tubules is due to the large amount of sodium absorbed and medullary tubules exist in a hypertonic sodium environment. To sodium stress the tissue, mouse kidney slices were exposed to monensin to allow passive entry of sodium ions from isotonic media and in separate studies, 400 and 600 mOsm NaCl was used. [NO] was measured with microelectrodes. Monensin (10 μM) caused a sustained increase in medullary and cortical [NO] to ∼180% of control and 400 mOsm NaCl caused a similar initial increase in [NO] that then subsided. 600 mOsm NaCl caused a more sustained increase in [NO] of >250% of control. L-NAME strongly attenuated the increased [NO] during sodium stress. The increase in [NO] during NaCl elevation was due to sodium ions because mannitol hyperosmolarity caused ∼20% of the increase in [NO]. Entry of sodium during NaCl hyperosmolarity was through bumetanide sensitive channels because the drug suppressed increased [NO]. Blockade of the sodium/calcium ion exchanger strongly suppressed the increased [NO] during monensin, to increase sodium entry into cells, and the elevated NaCl concentration. The data support a sodium-NO linkage that increased NO signaling in proportion to sodium stress by cortical tubules and was highly dependent upon sodium-calcium exchange.

Original languageEnglish (US)
Pages (from-to)33-43
Number of pages11
JournalNitric Oxide - Biology and Chemistry
Issue number1
StatePublished - Aug 2007


  • Hyperosmolarity
  • Kidney
  • Monensin
  • Nitric oxide
  • Tubules

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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