AJP - Renal Physiology, Vol 267, Issue 1 190-F195, Copyright © 1994 by American Physiological Society

ARTICLES

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

H. Tsukahara, Y. Krivenko, L. C. Moore and M. S. Goligorsky
Department of Medicine, Health Sciences Center, State University of New York, Stony Brook 11794-8152.

It has been hypothesized that fluctuations of the ionic composition in the interstitium of juxtaglomerular apparatus (JGA) modulate the function of extraglomerular 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+]; 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 examined 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.

This article has been cited by other articles:

				A. Just Mechanisms of renal blood flow autoregulation: dynamics and contributions Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R1 - R17. [Abstract] [Full Text] [PDF]

				R. Loutzenhiser, K. Griffin, G. Williamson, and A. Bidani Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2006; 290(5): R1153 - R1167. [Abstract] [Full Text] [PDF]

				A. Just, H. Ehmke, L. Toktomambetova, and H. R. Kirchheim Dynamic characteristics and underlying mechanisms of renal blood flow autoregulation in the conscious dog Am J Physiol Renal Physiol, June 1, 2001; 280(6): F1062 - F1071. [Abstract] [Full Text] [PDF]

				A. Just, H. Ehmke, U. Wittmann, and H. R. Kirchheim Tonic and phasic influences of nitric oxide on renal blood flow autoregulation in conscious dogs Am J Physiol Renal Physiol, March 1, 1999; 276(3): F442 - F449. [Abstract] [Full Text] [PDF]

				L. Balsam and N. Nikbakht L-Arginine inhibits vasopressin-stimulated mesangial cell Ca2+ Am J Physiol Cell Physiol, August 1, 1998; 275(2): C352 - C357. [Abstract] [Full Text] [PDF]

				J. D. STOCKAND and S. C. SANSOM Glomerular Mesangial Cells: Electrophysiology and Regulation of Contraction Physiol Rev, July 1, 1998; 78(3): 723 - 744. [Abstract] [Full Text] [PDF]

				J. Schnermann Juxtaglomerular cell complex in the regulation of renal salt excretion Am J Physiol Regulatory Integrative Comp Physiol, February 1, 1998; 274(2): R263 - R279. [Abstract] [Full Text] [PDF]

				B. Tonshoff, F. J. Kaskel, and L. C. Moore Effects of insulin-like growth factor I on the renal juxtamedullary microvasculature Am J Physiol Renal Physiol, January 1, 1998; 274(1): F120 - F128. [Abstract] [Full Text] [PDF]