The Role of Aldosterone in Vascular Permeability in Diabetes

More than 30% of diabetic patients develop dermatopathies linked to inflammation and increased vascular permeability. Considering the role of the renin-angiotensin-aldosterone system (RAAS) in diabetic complications, this study examined whether aldosterone (ALDO) and the mineralocorticoid receptor (MR) contribute to diabetes-related skin microangiopathy. Vascular permeability was measured in normoglycemic rats and insulin-dependent (streptozotocin-induced) diabetic rats. The expression of MR, 11β-hydroxysteroid dehydrogenase type 2 (HSD11β2), vascular endothelial growth factor (VEGF), von Willebrand factor (vWF), and the tight junction protein ZO-1 was determined by PCR and immunohistochemistry. Diabetic rats received the MR antagonist eplerenone (EPL, 100 mg/kg) for 10 days. Additionally, the effects of ALDO and EPL on endothelial permeability were evaluated in human dermal microvascular endothelial cells (HMEC-1) using a Transwell system. Diabetic rats showed skin atrophy, collagen damage, elevated ALDO levels, reduced MR and HSD11β2 expression, and increased vascular permeability, along with upregulation of VEGF and vWF. EPL markedly reduced these abnormalities. In vitro, ALDO increased endothelial permeability under hyperglycemia, and EPL counteracted this effect. These findings indicate that activation of the ALDO/MR pathway promotes skin vascular permeability in diabetes through VEGF- and vWF-dependent mechanisms. MR blockade limits these changes, suggesting therapeutic potential in preventing diabetes-associated skin complications.