Abstract
Reactive oxygen species are profoundly important for many physiologic functions and are also pivotal to numerous disease processes, particularly those involving inflammation. Much evidence has accrued demonstrating that aldosterone acts locally in many cells aside from those in the cortical collecting duct. Peripheral blood monocytes and vascular smooth muscle cells are both influenced by aldosterone to produce reactive oxygen species. This production contributes to nuclear factor kappaB (NF-κ B) activation and the genes regulated by this transcription factor. Aldosterone thereby plays an important role in atherosclerosis and hypertension-induced vascular injury. Aldosterone interacts with angiotensin (Ang) II-induced signaling. Both aldosterone and Ang II initiate ERK1/2 and JNK signaling; the effects of the two compounds is additive and involves the epidermal growth factor receptor. Recent data suggest that reactive oxygen species, might contribute to aldosterone production in nonadrenal tissues. A novel oxidized derivative of linoleic acid is a prime candidate in this regard. Oxidative stress may impair mineralocorticoid receptor function by inhibiting aldosterone binding. The latter finding has particularly important implications for elderly persons who exhibit increased oxidative stress and who are at risk for diminished aldosterone function in the distal nephron and subsequent hyperkalemia.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Keidar S, Kaplan M, Pavlotzky E, Coleman R, Hayek T, Hamoud S, Aviram M. Aldosterone administration to mice stimulates macrophage NADPH oxidase and increases atherosclerosis development: A possible role for angiotensin-converting enzyme and the receptors for angiotensin II and aldosterone. Circulation 2004;109:2213–2220.
Fujisawa G, Ishikawa S, Tsuboi Y, Okada K, Saito T. Therapeutic efficacy of non-peptide ADH antagonist OPC-31260 in SIADH rats. Kidney Int 1993;44:19–23.
Schulze PC, Yoshioka J, Takahashi T, He Z, King GL, Lee RT. Hyperglycemia promotes oxidative stress through inhibition of thioredoxin function by thioredoxin-interacting protein. J Biol Chem 2004;279:30369–30374.
Nishiyama A, Yao L, Nagai Y, Miyata K, Yoshizumi M, Kagami S, Kondo S, Kiyomoto H, Shokoji T, Kimura S, Kohno M, Abe Y. Possible contributions of reactive oxygen species and mitogen-activated protein kinase to renal injury in aldosterone/salt-induced hypertensive rats. Hypertension 2004;43:841–848.
Ahokas RA, Warrington KJ, Gerling IC, Sun Y, Wodi LA, Herring PA, Lu L, Bhattacharya SK, Postlethwaite AE, Weber KT. Aldosteronism and peripheral blood mononuclear cell activation: A neuroendocrine-immune interface. Circ Res 2003;93:e124–e135.
Virdis A, Neves MF, Amiri F, Viel E, Touyz RM, Schiffrin EL. Spironolactone improves angiotensin-induced vascular changes and oxidative stress. Hypertension 2002;40:504–510.
Sun Y, Zhang J, Lu L, Chen SS, Quinn MT, Weber KT. Aldosterone-induced inflammation in the rat heart: Role of oxidative stress. Am J Pathol 2002;161:1773–1781.
Gerling IC, Sun Y, Ahokas RA, Wodi LA, Bhattacharya SK, Warrington KJ, Postlethwaite AE, Weber KT. Aldosteronism: An immunostimulatory state precedes proinflammatory/fibrogenic cardiac phenotype. Am J Physiol Heart Circ Physiol 2003;285:H813–H821.
Iglarz M, Touyz RM, Viel EC, Amiri F, Schiffrin EL. Involvement of oxidative stress in the profibrotic action of aldosterone: Interaction wtih the renin-angiotension system. Am J Hypertens 2004;17:597–603.
caloCalo LA, Zaghetto F, Pagnin E, Davis PA, De Mozzi P, Sartorato P, Martire G, Fiore C, Armanini D. Effect of aldosterone and glycyrrhetinic acid on the protein expression of PAI-1 and p22(phox) in human mononuclear leukocytes. J Clin Endocrinol Metab 2004;89:1973–1976.
Pu Q, Neves MF, Virdis A, Touyz RM, Schiffrin EL. Endothelin antagonism on aldosterone-induced oxidative stress and vascular remodeling. Hypertension 2003;42:49–55.
Schiffrin EL, Gutkowska J, Genest J. Effect of angiotensin II and deoxycorticosterone infusion on vascular angiotensin II receptors in rats. Am J Physiol 1984;246: H608–H614.
Keidar S, Hayek T, Kaplan M, Pavlotzky E, Hamoud S, Coleman R, Aviram M. Effect of eplerenone, a selective aldosterone blocker, on blood pressure, serum and macrophage oxidative stress, and atherosclerosis in apolipoprotein E-deficient mice. J Cardiovasc Pharmacol 2003;41:955–963.
Fiebeler A, Schmidt F, Muller DN, Park JK, Dechend R, Bieringer M, Shagdarsuren E, Breu V, Haller H, Luft FC. Mineralocorticoid receptor affects AP-1 and nuclear factor-kappab activation in angiotensin II-induced cardiac injury. Hypertension 2001;37:787–793.
Mazak I, Fiebeler A, Muller DN, Park JK, Shagdarsuren E, Lindschau C, Dechend R, Viedt C, Pilz B, Haller H, Luft FC. Aldosterone potentiates angiotensin II-induced signaling in vascular smooth muscle cells. Circulation 2004;109:2792–2800.
Seshiah PN, Weber DS, Rocic P, Valppu L, Taniyama Y, Griendling KK. Angiotensin II stimulation of NAD(P)H oxidase activity: Upstream mediators. Circ Res 2002;91:406–413.
Weber DS, Taniyama Y, Rocic P, Seshiah PN, Dechert MA, Gerthoffer WT, Griendling KK. Phosphoinositide-dependent kinase 1 and p21-activated protein kinase mediate reactive oxygen species-dependent regulation of platelet-derived growth factor-induced smooth muscle cell migration. Circ Res 2004;94:1219–1226.
Gekle M, Freudinger R, Mildenberger S, Silbernagl S. Aldosterone interaction with epidermal growth factor receptor signaling in MDCK cells. Am J Physiol Renal Physiol 2002;282:F669–F679.
Krug AW, Grossmann C, Schuster C, Freudinger R, Mildenberger S, Govindan MV, Gekle M. Aldosterone stimulates epidermal growth factor receptor expression. J Biol Chem 2003;278:43060–43066.
Krug AW, Schuster C, Gassner B, Freudinger R, Mildenberger S, Troppmair J, Gekle M. Human epidermal growth factor receptor-1 expression renders Chinese hamster ovary cells sensitive to alternative aldosterone signaling. J Biol Chem 2002;277:45892–45897.
Goodfriend TL, Ball DL, Egan BM, Campbell WB, Nithipatikom K. Epoxy-keto derivative of linoleic acid stimulates aldosterone secretion. Hypertension 2004;43:358–363.
Goodfriend TL, Calhoun DA. Resistant hypertension, obesity, sleep apnea, and aldosterone: Theory and therapy. Hypertension 2004;43:518–524.
Galigniana MD, Piwien-Pilipuk G. Comparative inhibition by hard and soft metal ions of steroid-binding capacity of renal mineralocorticoid receptor cross-linked to the 90-kDa heat-shock protein heterocomplex. Biochem J 1999;341 (Pt 3):585–592.
Piwien-Pilipuk G, Galigniana MD. Oxidative stress induced by L-buthionine-(S,R)-sulfoximine, a selective inhibitor of glutathione metabolism, abrogates mouse kidney mineralocorticoid receptor function. Biochim Biophys Acta 2000;1495:263–280.
Piwien-Pilipuk G, Ayala A, Machado A, Galigniana MD. Impairment of mineralocorticoid receptor (MR)-dependent biological response by oxidative stress and aging: Correlation with post-translational modification of MR and decreased ADP-ribosylatable level of elongating factor 2 in kidney cells. J Biol Chem 2002;277:11896–11903.
Funder JW. Aldosterone, mineralocorticoid receptors and vascular inflammation. Mol Cell Endocrinol 2004;217:263–269.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Fiebeler, A., Luft, F.C. The Mineralocorticoid Receptor and Oxidative Stress. Heart Fail Rev 10, 47–52 (2005). https://doi.org/10.1007/s10741-005-2348-y
Issue Date:
DOI: https://doi.org/10.1007/s10741-005-2348-y