There is accumulating evidence that mineralocorticoids not only act on kidney but also on the cardiovascular system. We investigated the response of human umbilical venous endothelial cells (HUVECs) to aldosterone at a time scale of 20 minutes in absence and presence of the aldosterone antagonist spironolactone or other transport inhibitors. We applied atomic force microscopy (AFM), which measures cell volume and volume shifts between cytosol and cell nucleus. We observed an immediate cell volume increase (about 10%) approximately 1 min after addition of aldosterone (0.1 µmol/l), approaching a maximum (about 18%) 10 min after aldosterone treatment. Cell volume returned to normal 20 min after hormone exposure. Spironolactone (1 µmol/l) or amiloride (1 µmol/l) prevented the late aldosterone-induced volume changes but not the immediate change observed 1 min after hormone exposure. AFM revealed nuclear swelling 5 min after aldosterone addition, followed by nuclear shrinkage 15 min later. The Na+/H+ exchange blocker cariporide (10 µmol/l) was ineffective. We conclude: (i) Aldosterone induces immediate (1 min) swelling independently of plasma membrane Na+ channels and intracellular mineralocorticoid receptors followed by late mineralocorticoid receptor- and Na+-channel-dependent swelling. (ii) Intracellular macromolecule shifts cause the changes in cell volume. (iii) Both amiloride and spironolactone may be useful for medical applications to prevent aldosterone-induced vasculopathies.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
R.W. Berliner G. Giebisch (2001) ArticleTitleRemembrances of renal potassium transport. J. Membrane Biol. 184 225–232 Occurrence Handle10.1007/s00232-001-0091-4 Occurrence Handle1:CAS:528:DC%2BD38XktlGqtw%3D%3D
G.A. Brown M.D. Vukovich E.R. Martini M.L. Kohut W.D. Franke D.A. Jackson D.S. King (2000) ArticleTitleEndocrine responses to chronic androstenedione intake in 30- to 56-year-old men. J. Clin. Endocrinol. Metab. 85 4074–4080 Occurrence Handle1:CAS:528:DC%2BD3cXotlWntbs%3D Occurrence Handle11095435
C.M. Doolan G.C. O’Sullivan B.J. Harvey (1998) ArticleTitleRapid effects of corticosteroids on cytosolic protein kinase C and intracellular calcium concentration in human distal colon. Mol. Cell Endocrinol. 138 71–79 Occurrence Handle10.1016/S0303-7207(98)00020-3 Occurrence Handle1:CAS:528:DyaK1cXjtVKksbo%3D Occurrence Handle9685216
D. Duprez M. De Buyzere E.R. Rietzschel D.L. Clement (2000) ArticleTitleAldosterone and vascular damage. Curr. Hypertens. Rep. 2 327–334 Occurrence Handle1:STN:280:DC%2BD3cvpsV2htA%3D%3D Occurrence Handle10981167
M. Epstein (2001) ArticleTitleAldosterone as a mediator of progressive renal disease: pathogenetic and clinical implications. Am. J. Kidney Dis. 37 677–688 Occurrence Handle1:CAS:528:DC%2BD3MXjtFWqs70%3D Occurrence Handle11273866
G. Frindt T. McNair A. Dahlmann E. Jacobs-Palmer L.G. Palmer (2002) ArticleTitleEpithelial Na channels and short-term renal response to salt deprivation. Am. J. Physiol. 283 F717–F726
N. Gamper S.M. Huber K. Badawi F. Lang (2000) ArticleTitleCell volume-sensitive sodium channels upregulated by glucocorticoids in U937 macrophages. Pfluegers Arch. 441 281–286 Occurrence Handle10.1007/s004240000410 Occurrence Handle1:CAS:528:DC%2BD3cXos1KhtLc%3D
M. Gekle N. Golenhofen H. Oberleithner S. Silbernagl (1996) ArticleTitleRapid activation of Na+/H+ exchange by aldosterone in renal epithelial cells requires Ca2+ and stimulation of a plasma membrane proton conductance. Proc. Natl. Acad. Sci USA 93 10500–10504 Occurrence Handle10.1073/pnas.93.19.10500 Occurrence Handle1:CAS:528:DyaK28XlslGrs7o%3D Occurrence Handle8816833
T. Goerge A. Niemeyer P. Rogge R. Ossig H. Oberleithner S.W. Schneider (2002) ArticleTitleSecretion pores in human endothelial cells during acute hypoxia. J. Membrane Biol. 187 203–211 Occurrence Handle10.1007/s00232-001-0164-4 Occurrence Handle1:CAS:528:DC%2BD38Xks1ylsrs%3D
N. Golestaneh C. Klein F. Valamanesh G. Suarez M.K. Agarwal M. Mirshahi (2001) ArticleTitleMineralocorticoid receptor-mediated signaling regulates the ion gated sodium channel in vascular endothelial cells and requires an intact cytoskeleton. Biochem. Biophys. Res. Commun. 280 1300–1306 Occurrence Handle10.1006/bbrc.2001.4275 Occurrence Handle1:CAS:528:DC%2BD3MXptlCrtQ%3D%3D Occurrence Handle11162670
H. Hatakeyama I. Miyamori T. Fujita Y. Takeda R. Takeda H. Yamamoto (1994) ArticleTitleVascular aldosterone. Biosynthesis and a link to angiotensin II-induced hypertrophy of vascular smooth muscle cells. J. Biol. Chem. 269 24316–24320 Occurrence Handle1:CAS:528:DyaK2cXmt1elsro%3D Occurrence Handle7929089
H. Hayashi K. Szaszi S. Grinstein (2002) ArticleTitleMultiple modes of regulation of Na+/H+ exchangers. Ann. N. Y. Acad. Sci. 976 248–258 Occurrence Handle1:CAS:528:DC%2BD3sXht1yhsro%3D Occurrence Handle12502567
E.A. Jaffe R.L. Nachman C.G. Becker C.R. Minick (1973) ArticleTitleCulture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J. Clin. Invest 52 2745–2756 Occurrence Handle1:STN:280:CSuD387mtlw%3D Occurrence Handle4355998
P. Lijnen V. Petrov (2000) ArticleTitleInduction of cardiac fibrosis by aldosterone. J. Mol. Cell Cardiol. 32 865–879 Occurrence Handle10.1006/jmcc.2000.1129 Occurrence Handle1:CAS:528:DC%2BD3cXkvVOrsr0%3D Occurrence Handle10888242
M. Lombes M.E. Oblin J.M. Gasc E.E. Baulieu N. Farman J.P. Bonvalet (1992) ArticleTitleImmunohistochemical and biochemical evidence for a cardiovascular mineralocorticoid receptor. Circ. Res. 71 503–510 Occurrence Handle1:CAS:528:DyaK38Xls1Cis7k%3D Occurrence Handle1323429
W.J., II Meyer N.R. Nichols (1981) ArticleTitleMineralocorticoid binding in cultured smooth muscle cells and fibroblasts from rat aorta. J. Steroid Biochem. 14 1157–1168 Occurrence Handle10.1016/0022-4731(81)90046-7 Occurrence Handle1:CAS:528:DyaL38XhtlKisb8%3D Occurrence Handle6273655
G. Miric C. Dallemagne Z. Endre S. Margolin S.M. Taylor L. Brown (2001) ArticleTitleReversal of cardiac and renal fibrosis by pirfenidone and spironolactone in streptozotocin-diabetic rats. Br. J. Pharmacol. 133 687–694 Occurrence Handle1:CAS:528:DC%2BD3MXlsVCrtLg%3D Occurrence Handle11429393
J. Nielsen T.H. Kwon S. Masilamani K. Beutler H. Hager S. Nielsen M.A. Knepper (2002) ArticleTitleSodium transporter abundance profiling in kidney: effect of spironolactone. Am. J. Physiol. 283 F923–F933
H. Oberleithner J. Reinhardt H. Schillers P. Pagel S.W. Schneider (2000) ArticleTitleAldosterone and nuclear volume cycling. Cell Physiol. Biochem. 10 429–434 Occurrence Handle10.1159/000016379 Occurrence Handle1:CAS:528:DC%2BD3MXjt1aks7g%3D Occurrence Handle11125225
H. Oberleithner M. Weigt H.-J. Westphale W. Wang (1987) ArticleTitleAldosterone activates Na+/H+ exchange and raises cytoplasmic pH in target cells of the amphibian kidney. Proc. Natl. Acad. Sci. USA 84 1464–1468 Occurrence Handle1:CAS:528:DyaL2sXhsV2ku70%3D Occurrence Handle3029782
J.A. Oliver Q. Al Awqati (1998) ArticleTitleAn endothelial growth factor involved in rat renal development. J. Clin. Invest. 102 1208–1219 Occurrence Handle1:CAS:528:DyaK1cXmtFyhsbo%3D Occurrence Handle9739055
E.A. Palmieri B. Biondi S. Fazio (2002) ArticleTitleAldosterone receptor blockade in the management of heart failure. Heart Fail. Rev. 7 205–219 Occurrence Handle10.1023/A:1015336831407 Occurrence Handle1:CAS:528:DC%2BD38XkvVWqurg%3D Occurrence Handle11988643
S. Rajagopalan D. Duquaine S. King B. Pitt P. Patel (2002) ArticleTitleMineralocorticoid receptor antagonism in experimental atherosclerosis. Circulation 105 2212–2216 Occurrence Handle10.1161/01.CIR.0000015854.60710.10 Occurrence Handle1:CAS:528:DC%2BD38XktlOku7Y%3D Occurrence Handle11994257
B.C. Rossier (2002) ArticleTitleHormonal regulation of the epithelial sodium channel ENaC: N or P(o)? J. Gen. Physiol. 120 67–70 Occurrence Handle10.1085/jgp.20028638 Occurrence Handle1:CAS:528:DC%2BD38XlslOhsLk%3D Occurrence Handle12084776
C. Schafer V. Shahin L. Albermann M.J. Hug J. Reinhardt H. Schillers S.W. Schneider H. Oberleithner (2002) ArticleTitleAldosterone signaling pathway across the nuclear envelope. Proc. Natl. Acad. Sci. USA 99 7154–7159 Occurrence Handle10.1073/pnas.092140799 Occurrence Handle1:CAS:528:DC%2BD38XjvFCqu7s%3D Occurrence Handle11983859
M. Schneider A. Ulsenheimer M. Christ M. Wehling (1997a) ArticleTitleNongenomic effects of aldosterone on intracellular calcium in porcine endothelial cells. Am. J. Physiol 272 E616–E620 Occurrence Handle1:CAS:528:DyaK2sXjt1Kqt7c%3D
S.W. Schneider Y. Yano B.E. Sumpio B.P. Jena J.P. Geibel M. Gekle H. Oberleithner (1997b) ArticleTitleRapid aldosterone-induced cell volume increase of endothelial cells measured by the atomic force microscope. Cell Biol. Int. 21 759–768 Occurrence Handle1:CAS:528:DyaK1cXmslCgurk%3D
J.S. Silvestre V. Robert C. Heymes B. Aupetit-Faisant C. Mouas J.M. Moalic B. Swynghedauw C. Delcayre (1998) ArticleTitleMyocardial production of aldosterone and corticosterone in the rat. Physiological regulation. J. Biol. Chem. 273 4883–4891 Occurrence Handle10.1074/jbc.273.9.4883 Occurrence Handle1:CAS:528:DyaK1cXhs1Cgtbw%3D Occurrence Handle9478930
C.T. Stier Jr P.N. Chander R. Rocha (2002) ArticleTitleAldosterone as a mediator in cardiovascular injury. Cardiol. Rev. 10 97–107 Occurrence Handle10.1097/00045415-200203000-00008 Occurrence Handle11895576
J.B. Stokes (1999) ArticleTitleDisorders of the epithelial sodium channel: insights into the regulation of extracellular volume and blood pressure. Kidney Int. 56 2318–2333 Occurrence Handle10.1046/j.1523-1755.1999.00803.x Occurrence Handle1:CAS:528:DC%2BD3cXisVCgsw%3D%3D Occurrence Handle10594813
J.D. Symons S. Schaefer (2001) ArticleTitleNa(+)/H(+) exchange subtype 1 inhibition reduces endothelial dysfunction in vessels from stunned myocardium. Am. J. Physiol. 281 H1575–H1582 Occurrence Handle1:CAS:528:DC%2BD3MXnsVyqtLo%3D
Y. Takeda I. Miyamori T. Yoneda K. Iki H. Hatakeyama I.A. Blair F.Y. Hsieh R. Takeda (1995) ArticleTitleProduction of aldosterone in isolated rat blood vessels. Hypertension 25 170–173 Occurrence Handle1:CAS:528:DyaK2MXkvF2gt7w%3D Occurrence Handle7843766
Y. Takeda T. Yoneda M. Demura I. Miyamori H. Mabuchi (2000) ArticleTitleSodium-induced cardiac aldosterone synthesis causes cardiac hypertrophy. Endocrinology 141 1901–1904 Occurrence Handle1:CAS:528:DC%2BD3cXlt1Wnsbs%3D Occurrence Handle10803602
K.T. Weber C.G. Brilla (1991) ArticleTitlePathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system. Circulation 83 1849–1865 Occurrence Handle1:STN:280:By6B2cbkt1A%3D Occurrence Handle1828192
M. Wehling J. Kasmayr K. Theisen (1989) ArticleTitleFast effects of aldosterone on electrolytes in human lymphocytes are mediated by the sodium-proton-exchanger of the cell membrane. Biochem. Biophys. Res. Commun. 164 961–967 Occurrence Handle1:CAS:528:DyaK3cXptVE%3D Occurrence Handle2556129
We thank Mrs. Marianne Wilhelmi and Hannelore Arnold for their excellent HUVEC culture work. We thank Drs. Kleemann and Lang (Aventis Pharma GmbH, Deutschland) for kindly providing cariporide. The study was supported by IZKF Münster (Project A9) and the Volkswagenstiftung (Project BD 151103).
About this article
Cite this article
Oberleithner, H., Schneider, S., Albermann, L. et al. Endothelial Cell Swelling by Aldosterone . J. Membrane Biol. 196, 163–172 (2003). https://doi.org/10.1007/s00239-003-0635-6
- Atomic force microscopy
- Na+ channel