Endothelial cell swelling by aldosterone

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 mumol/l), approaching a maximum (about 18%) 10 min after aldosterone treatment. Cell volume returned to normal 20 min after hormone exposure. Spironolactone (1 mumol/l) or amiloride (1 mumol/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 mumol/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.