Aldosterone causes nongenomic vasoconstriction by activating phospholipase C in preglomerular afferent arterioles. 18 The endothelium may modulate this vasoconstrictor effect by NO release. 19 Aldosterone induced a dose-dependent vasoconstriction in microperfused rabbit afferent arterioles, which was enhanced by disrupting the endothelium. Inhibition of NO synthase induced a similar effect, which was inhibited by chelerythrine, a protein kinase (PKC) inhibitor. Thapsigargin, or dantrolene, which blocks inositol 1, 4, 5-triphosphate (inositol triphosphate)–induced intracellular calcium release, attenuated the effect of aldosterone. Thus, these data show that endothelium-derived NO modulates the vasoconstrictor actions of aldosterone in preglomerular afferent arterioles that are mediated by the activation of inositol triphosphate and PKC pathways.

Using atomic force microscopy, Oberleithner et al20 demonstrated that aldosterone induced increases of the cell nucleus of endothelial cells that could reach 15% to 28% of total cell volume in 10 minutes, effects which disappeared within 30 minutes. They postulated that aldosterone-induced nuclear swelling was a rapid genomic effect, because receptors translocated from the cytoplasm into the nucleus, and gene transcription followed, with a return of nuclear volume to normal when mRNA was exported into the cytoplasm. These authors concluded that endothelial responses to aldosterone could not be divided into acute nongenomic (10 minutes) and sustained genomic (10 minutes) effects, because rapid genomic effects also occurred. They also demonstrated that cultured human umbilical vein endothelial cells responded to aldosterone with sodium and water entry and swelling that was blocked by spironolactone. 21 Swollen aldosterone-treated endothelial cells shrunk when amiloride was applied at concentrations that do not inhibit the sodium-proton exchanger (NHE) or with cariporide, a selective inhibitor of NHE, indicating that a sodium channel similar to the epithelial sodium channel of the distal nephron was involved in this aldosterone effect. Amiloride hyperpolarizes the cell as a result of the blockade of sodium channels, inducing chloride and water efflux, and cell shrinking. Oberleithner et al20 suggested that because the surface of the endothelium is huge, aldosterone may reduce serum concentrations of potassium by this action and not only by its renal effects. They additionally proposed that aldosterone-induced endothelial cell swelling could increase peripheral resistance. Recently, Oberleithner22 showed that aldosterone remodels human endothelium in vitro, increasing cell size and rigidity, with protein leakage through intercellular gaps that may be the result of increased apical membrane tension. Thus, this author concluded that aldosterone makes human endothelium stiff and vulnerable, which could contribute to endothelial dysfunction.