Nitric oxide production by mouse renal tubules can be increased by a sodium-dependent mechanism. Nitric Oxide 2007 Aug;17(1):33-43
Date
07/03/2007Pubmed ID
17604190Pubmed Central ID
PMC2045156DOI
10.1016/j.niox.2007.05.002Scopus ID
2-s2.0-34447303515 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
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 microM) caused a sustained increase in medullary and cortical [NO] to approximately 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 approximately 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.
Author List
Kempson S, Thompson N, Pezzuto L, Glenn Bohlen HAuthor
Nathan Thompson MD Associate Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsKidney
Kidney Tubules
Kidney Tubules, Proximal
Male
Mannitol
Mice
Models, Biological
Monensin
NG-Nitroarginine Methyl Ester
Nitric Oxide
Sodium
Sodium Chloride
Sodium-Calcium Exchanger