Aldosterone remodels human endothelium.
OBJECTIVE
In response to aldosterone endothelial cells swell and stiffen. Although amiloride-sensitive sodium and water uptake is known to be involved, the underlying mechanisms are yet unclear. We tested the hypothesis whether the intracellular accumulation of water or organic matter is responsible for the structural and functional alterations.


METHODS
Atomic force microscopy was used as an imaging tool and a mechanical nanosensor. Cell water, organic cell matter and cell pressure was measured at single cell level in human umbilical vein endothelial cells (HUVEC). Furthermore, we tested by means of a miniature perfusion chamber in vitro the physical robustness to blood flow of the aldosterone-treated endothelium.


RESULTS
In response to a three-day treatment with 1 nM aldosterone HUVEC swell. To our surprise, cell water decreased from 82+/-6% to 71+/-5% while intracellular organic matter increased from 18+/-1.8% to 29+/-3.0%. These changes were paralleled by a rise in cell pressure of 114%, measured in living HUVEC in vitro. Blood flow across the endothelium was found significantly altered after aldosterone treatment. Imaging the endothelial monolayer after blood perfusion disclosed large gaps between cells treated with aldosterone. The mineralocorticoid receptor blockers, spironolactone and eplerenone could prevent the aldosterone actions.


CONCLUSIONS
Mild aldosteronism causes intracellular accumulation of organic matter at the cost of cell water. This makes endothelium stiff and vulnerable to shear stress. The measurements could explain clinical observations that high blood pressure combined with high plasma aldosterone concentration may damage the endothelium of blood vessels.
Oberleithner
H
H
Institute of Physiology II, University Münster, Germany. oberlei@uni-muenster.de
Riethmüller
C
C
Ludwig
T
T
Hausberg
M
M
Schillers
H
H
D000450:Aldosterone / Q000494:pharmacology*; D000704:Analysis of Variance; D001692:Biological Transport; D048429:Cell Size; D002478:Cells, Cultured; D004548:Elasticity; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism*; D000077545:Eplerenone; D006801:Humans; D006929:Hyperaldosteronism / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D008901:Mineralocorticoids / Q000494:pharmacology; D011312:Pressure; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D014471:Umbilical Veins; D014882:Water-Electrolyte Balance
D008901:Mineralocorticoids; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone