AJP - Cell Physiology, Vol 257, Issue 4 C629-C636, Copyright © 1989 by American Physiological Society

ARTICLES

Mechanism of angiotensin II stimulation of Na-K-Cl cotransport of vascular smooth muscle cells

N. E. Owen and K. M. Ridge
Department of Biological Chemistry and Structure, University of Health Sciences, Chicago Medical School, Illinois 60064.

Previous studies from this laboratory have demonstrated that Na-K-Cl cotransport of vascular smooth muscle cells is inhibited by hormones that increase intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels (e.g., catecholamines) and is stimulated by hormones that increase intracellular guanosine 3',5'-cyclic monophosphate (cGMP) levels (e.g., atrial natriuretic peptides). Others have suggested that calcium may also modulate Na-K-Cl cotransport of vascular smooth muscle cells. The goal of the present study was to characterize the mechanism of angiotensin II stimulation of Na-K-Cl cotransport of early passage cultured vascular smooth muscle cells. We found that when vascular smooth muscle cells were treated with angiotensin II or a calcium ionophore, Na-K-Cl cotransport was markedly enhanced above basal levels. We found that when calcium influx was blocked with the calcium chelator EDTA or with three different chemical types of calcium-channel blockers, the stimulatory effects of angiotensin II on Na-K-Cl cotransport were markedly inhibited. Furthermore, when intracellular calcium mobilization was blocked with high concentrations of the calcium chelator quin2 or with the intracellular calcium antagonist 8-(diethyl-amino)octyl 3,4,5-trimethoxybenzoate (TMB-8), the stimulatory effects of angiotensin II on Na-K-Cl cotransport were also substantially inhibited. These results suggest that both calcium influx via receptor-operated calcium channels and intracellular calcium mobilization may play a role in stimulation of Na-K-Cl cotransport of vascular smooth muscle cells in response to angiotensin II.

This article has been cited by other articles:

				J. W. Meyer, M. Flagella, R. L. Sutliff, J. N. Lorenz, M. L. Nieman, C. S. Weber, R. J. Paul, and G. E. Shull Decreased blood pressure and vascular smooth muscle tone in mice lacking basolateral Na+-K+-2Cl- cotransporter Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1846 - H1855. [Abstract] [Full Text] [PDF]

				J. M. Russell Sodium-Potassium-Chloride Cotransport Physiol Rev, January 1, 2000; 80(1): 211 - 276. [Abstract] [Full Text] [PDF]

				M. Flagella, L. L. Clarke, M. L. Miller, L. C. Erway, R. A. Giannella, A. Andringa, L. R. Gawenis, J. Kramer, J. J. Duffy, T. Doetschman, et al. Mice Lacking the Basolateral Na-K-2Cl Cotransporter Have Impaired Epithelial Chloride Secretion and Are Profoundly Deaf J. Biol. Chem., September 17, 1999; 274(38): 26946 - 26955. [Abstract] [Full Text] [PDF]

				F. Akar, E. Skinner, J. D. Klein, M. Jena, R. J. Paul, and W. C. O'Neill Vasoconstrictors and nitrovasodilators reciprocally regulate the Na+-K+-2Cl- cotransporter in rat aorta Am J Physiol Cell Physiol, June 1, 1999; 276(6): C1383 - C1390. [Abstract] [Full Text] [PDF]

				G. Kovacs, J. Peti-Peterdi, L. Rosivall, and P. D. Bell Angiotensin II directly stimulates macula densa Na-2Cl-K cotransport via apical AT1 receptors Am J Physiol Renal Physiol, February 1, 2002; 282(2): F301 - F306. [Abstract] [Full Text] [PDF]