This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shah, J. R. Articles by Hamlyn, J. M. Search for Related Content PubMed PubMed Citation Articles by Shah, J. R. Articles by Hamlyn, J. M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB DIGOXIN OUABAIN

(Hypertension. 1999;33:373-377.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Effects of Angiotensin II on Sodium Potassium Pumps, Endogenous Ouabain, and Aldosterone in Bovine Zona Glomerulosa Cells

Jui R. Shah; James Laredo; Bruce P. Hamilton; John M. Hamlyn

From the Departments of Physiology (J.R.S., J.M.H., J.L.) and Medicine (B.P.H.), University of Maryland, and Veterans Administration Medical Center (B.P.H.), Baltimore, Md.

Correspondence to Jui R. Shah, PhD, Department of Physiology, School of Medicine, University of Maryland at Baltimore, 655 W Baltimore St, Baltimore, MD 21201. E-mail jshah{at}umaryland.edu

Abstract—Angiotensin (Ang) II stimulates secretions of aldosterone and an endogenous ouabain-like steroid (EO) from bovine adrenal zona glomerulosa (BAG) cells. The BAG cell sodium pump, a possible target of EO, affects aldosterone secretion although little is known about this pump. Here, we describe the effects of Ang II on the characteristics of this transporter and steroid secretions. Under serum-free conditions, ³H-ouabain bound to a single class of sites on BAG cells. Binding of label was time and concentration dependent, was sensitive to extracellular potassium ions, and was displaced by ouabain and digoxin with EC₅₀ of 218 and 232 nmol/L, respectively. Sodium pump–mediated ⁸⁶Rb uptake was inhibited by ouabain (EC₅₀ 301 nmol/L). Ang II dose dependently augmented secretions of EO and aldosterone, increased ouabain-sensitive ⁸⁶Rb uptake and ³H-ouabain binding, and increased the affinity for ³H-ouabain binding (K_d, from 205 to 80 nmol/L) with no change in the maximal number of sodium pumps (5.45x10⁶) per cell. Losartan blocked all effects of Ang II except EO secretion, which was inhibited by PD123319. We conclude that BAG cells express sodium pumps in high density and bind ouabain to a single class of low-affinity sites. The characteristics of the sodium pumps protect BAG cells from EO autotoxicity but may exclude them from mediating feedback inhibition of EO secretion. The effects of Ang II on sodium pump activity, ouabain binding affinity, and aldosterone secretion are mediated via Ang II type 1 receptors, whereas Ang II type 2 receptors augment EO secretion. The role of the Ang II–mediated increase in the ouabain sensitivity of BAG cell sodium pumps in the secretions of aldosterone and EO remains to be elucidated.

Key Words: cardiac glycosides • adrenal • Na,K-ATPase • secretion • cell culture

This article has been cited by other articles:

				A. Y. Bagrov, J. I. Shapiro, and O. V. Fedorova Endogenous Cardiotonic Steroids: Physiology, Pharmacology, and Novel Therapeutic Targets Pharmacol. Rev., March 1, 2009; 61(1): 9 - 38. [Abstract] [Full Text] [PDF]

				E. Shibata, R. W. Powers, A. Rajakumar, F. von Versen-Hoynck, M. J. Gallaher, D. L. Lykins, J. M. Roberts, and C. A. Hubel Angiotensin II decreases system A amino acid transporter activity in human placental villous fragments through AT1 receptor activation Am J Physiol Endocrinol Metab, November 1, 2006; 291(5): E1009 - E1016. [Abstract] [Full Text] [PDF]

				H. M.A.M. Qazzaz, Z. Cao, D. D. Bolanowski, B. J. Clark, and R. Valdes Jr De Novo Biosynthesis and Radiolabeling of Mammalian Digitalis-Like Factors Clin. Chem., March 1, 2004; 50(3): 612 - 620. [Abstract] [Full Text] [PDF]

				M. A. El-Masri, B. J. Clark, H. M. Qazzaz, and R. Valdes Jr Human Adrenal Cells in Culture Produce Both Ouabain-like and Dihydroouabain-like Factors Clin. Chem., October 1, 2002; 48(10): 1720 - 1730. [Abstract] [Full Text] [PDF]

				R. I. Dmitrieva and P. A. Doris Cardiotonic Steroids: Potential Endogenous Sodium Pump Ligands with Diverse Function Experimental Biology and Medicine, September 1, 2002; 227(8): 561 - 569. [Abstract] [Full Text] [PDF]

				Y. Hou and N. A. Delamere Influence of ANG II on cytoplasmic sodium in cultured rabbit nonpigmented ciliary epithelium Am J Physiol Cell Physiol, August 1, 2002; 283(2): C552 - C559. [Abstract] [Full Text] [PDF]

				H. Wang and F. H.H. Leenen Brain Sodium Channels Mediate Increases in Brain "Ouabain" and Blood Pressure in Dahl S Rats Hypertension, July 1, 2002; 40(1): 96 - 100. [Abstract] [Full Text] [PDF]