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(Hypertension. 1999;33:1025-1030.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Local Renin-Angiotensin System Is Involved in K⁺-Induced Aldosterone Secretion from Human Adrenocortical NCI-H295 Cells

Urte Hilbers; Jörg Peters; Stefan R. Bornstein; Fernando M. A. Correa; Olaf Jöhren; Juan M. Saavedra; Monika Ehrhart-Bornstein

From the Department of Internal Medicine III, University of Leipzig Germany (U.H.); the Department of Pharmacology, University of Heidelberg Germany (J.P.); the Section on Pharmacology, National Institute of Mental Health, Bethesda, Md (F.M.A.C., O.J., J.M.S.); and the National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md (S.R.B., M.E.-B.). Present address of F.M.A. Correa: Department of Pharmacology, School of Medicine of Ribeirao Preto, University of Sao Paolo, Brazil.

Correspondence to Monika Ehrhart-Bornstein, PhD, NICHD, NIH, Bldg 10, Room 10N262, 10 Center Dr, MSC 1862, Bethesda, MD 20892-1862. E-mail monika.eb{at}worldnet.att.com

Abstract—NCI-H295, a human adrenocarcinoma cell line, has been proposed as a model system to define the role of the renin-angiotensin system in the regulation of aldosterone production in humans. Because the precise cellular localization of the components of the renin-angiotensin system in human adrenal cortical cells remains unclear, we investigated their localization in this defined cell system. NCI-H295 cells expressed both angiotensinogen and renin as shown by reverse transcriptase polymerase chain reaction and immunohistochemistry. Human angiotensin-converting enzyme (ACE) was not detectable by immunocytochemistry, ACE binding, or reverse transcriptase polymerase chain reaction. However, 3.5 mmol/L K⁺ stimulated the formation of both angiotensin I and angiotensin II 1.9- and 2.5-fold, respectively, and increased aldosterone release 3.0-fold. The K⁺-induced stimulation of aldosterone release was decreased by captopril and enalaprilat (24% and 26%, respectively) and by the angiotensin type 1 (AT₁)-receptor antagonist losartan (28%). Angiotensin II–induced stimulation of aldosterone release was abolished by losartan treatment. Specific [¹²⁵I]Sar1-angiotensin II binding was detected by receptor autoradiography. The binding of [¹²⁵I]Sar¹-angiotensin II was completely displaced by the AT₁ antagonist losartan but not by the AT₂ receptor ligand PD 123319, confirming the expression of angiotensin II AT₁ receptors in NCI-H295 cells. Our results demonstrate that NCI-H295 cells express most of the components of the renin-angiotensin system. Our failure to detect ACE, however, suggests that the production of angiotensin II in NCI-H295 cells may be ACE independent. NCI-H295 cells are able to produce angiotensin II, and K⁺ increases aldosterone secretion in part through an angiotensin-mediated pathway. The production of angiotensin II in NCI-H295 cells demonstrates that this human cell line can be useful to characterize the role of locally produced angiotensin II in the regulation of aldosterone release.

Key Words: NCI-H295 cell line • renin-angiotensin system • angiotensin II • aldosterone • potassium

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