Decrease in ambient [Cl-] stimulates nitric oxide release from cultured rat mesangial cells

Hirokazu Tsukahara, Y. Krivenko, L. C. Moore, M. S. Goligorsky

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It has been hypothesized that fluctua-tions of the ionic composition in the interstitium of juxtaglo merular apparatus (JGA) modulate the function of extraglo merular mesangial cells (MC), thereby participating in tubuloglomerular feedback (TGF) signal transmission. We examined the effects of isosmotic reductions in ambient sodium concentration ([Na+]) and [Cl-] on cytosolic calcium concentration ([Ca2+]i) in cultured rat MC. Rapid reduction of [Na+] or [Cl-] in the bath induced a concentration-dependent rise in [Ca2+]i. MC are much more sensitive to decreases in ambient [Cl-] than to [Na+]i a decrease in [Cl-] as small as 14 mM was sufficient to elicit a detectable [Ca2+]i response. These observations suggest that MC can be readily stimulated by modest perturbations of extracellular [Cl-]. Next, we exam ined whether activation of MC by lowered ambient [Cl-] influences cellular nitric oxide (NO) production. Using an amperometric NO sensor, we found that a 13 mM decrease in ambient [Cl-] caused a rapid, Ca2+/calmodulin-dependent rise in NO release from MC. This response was not inhibitable by dexamethasone, indicating the involvement of the constitutive rather than the inducible type of NO synthase in MC. In addition, the NO release was blunted by indomethacin pretreatment, suggesting that a metabolite(s) of cyclooxygenase regulates the activation of NO synthase in MC. Our findings that small perturbations in external [Cl-] stimulate MC to release NO, a highly diffusible and rapidly acting vasodilator, provide a possible mechanism to explain the transmission of the signal for the TGF response within the JGA.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Issue number1 36-1
Publication statusPublished - 1994
Externally publishedYes



  • Amperometric nitric oxide sensor
  • Chloride ion concentration
  • Cytosolic calcium
  • Nitric oxide synthase
  • Tubuloglomerular feedback

ASJC Scopus subject areas

  • Physiology

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