Aldosterone activates endothelial exocytosis.
Although elevated levels of aldosterone are associated with vascular inflammation, the proinflammatory pathways of aldosterone are not completely defined. We now show that aldosterone triggers endothelial cell exocytosis, the first step in leukocyte trafficking. Exogenous aldosterone stimulates endothelial exocytosis of Weibel-Palade bodies, externalizing P-selectin and releasing von Willebrand factor. Spironolactone, a nonselective mineralocorticoid receptor (MR) blocker, antagonizes aldosterone-induced endothelial exocytosis. Knockdown of the MR also decreases exocytosis, suggesting that the MR mediates exocytosis. Aldosterone triggers exocytosis within minutes, and this effect is not inhibited by actinomycin D, suggesting a nongenomic effect of aldosterone. Aldosterone treatment of endothelial cells increases leukocyte adherence to endothelial cells in culture. Taken together, our data suggest that aldosterone activates vascular inflammation in part through nongenomic, MR-mediated pathways. Aldosterone antagonism may decrease vascular inflammation and cardiac fibrosis in part by blocking endothelial exocytosis.
Jeong
Youngtae
Y
Department of Medicine, Graduate Program in Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Chaupin
Damian F
DF
Matsushita
Kenji
K
Yamakuchi
Munekazu
M
Cameron
Scott J
SJ
Morrell
Craig N
CN
Lowenstein
Charles J
CJ
D000450:Aldosterone / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects*; D005089:Exocytosis / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism; D020302:Weibel-Palade Bodies / Q000187:drug effects / Q000378:metabolism
D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone