Abstract
Elevations in luminal sodium chloride concentration ([NaCl]L) alter macula densa (MD) intracellular calcium concentration and result in the release of nitric oxide (NO). Also, concomitant elevations in [NaCl]L and luminal osmolality (osmL) lead to shrinkage of macula densa cells, while increases in [NaCl]L at constant osmL produce cell swelling. Currently, there is little information concerning the intracellular signaling event that leads to the activation of MD NO synthase. Current studies were performed to determine whether changes in MD cell volume and/or calmodulin‐dependent signaling activate MD NO synthase. Thick ascending limb‐glomerulus preparations were isolated and perfused from rabbits, and MD NO release was detected with fluorescence microscopy using DAF‐FM. Elevations in [NaCl]L (from 0 to 150 mmol/L) at constant osmL produced an increase in DAF‐FM fluorescence of 5±0.5%, while concomitant elevations in [NaCl]L and osmL led to an increase of 12±0.7%. Luminal application of furosemide, a blocker of Na+:2Cl‐:K+ cotransport, reversed [NaCl]L‐dependent NO release (‐0.04±0.2%). Also, application of the calmodulin‐inhibitor calmidazolium blocked [NaCl]L‐dependent NO release (1.8±1.8%). Thus, [NaCl]L‐dependent NO production by MD cells may be modulated by changes in cell volume and requires activation of calmodulin signaling.
Published Version
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