Abstract 3537: Hyperaldosteronism And Altered Expression Of SGK 1 Dependent Sodium Transporter In Type 2 Diabetes Lead To Salt Dependency Of Blood Pressure
This study was designed to test whether altered aldosterone-related sodium handling leads to salt sensitive blood pressure (RR) in diabetes. As a model of type 2 diabetes Zucker Diabetic Fatty (ZDF) rats and as euglycemic controls Zucker lean (ZDL) rats were divided into groups receiving normal (0.28%) and high salt (5.5%) diet (ZDF+S, ZDL+S) for 10 weeks. RR was measured weekly by tail cuff method. MRNA expressions of serum and glucocorticoid induced kinase 1 (SGK1) and ENaC alpha sodium transporter were quantified by RT-qPCR. Vascular hypertrophy (media to lumen ratio, M:L) of mesenteric resistance arteries was assessed using a pressurized myograph. RR was significantly higher in ZDF+S vs. ZDF (146±2 vs 133±3 mmHg; p<0.05), while there was no difference between ZDL+S and ZDL (151±3 vs 147±3 mmHg). Plasma sodium concentration was higher in ZDF+S vs ZDF (144±3 vs 131±4 mmol/L), while there was no difference between ZDL+S and ZDL. Plasma aldosterone levels were higher in ZDF vs ZDL (191±23 vs 95±35 pg/ml; p<0.05). Aldosterone was decreased to zero in ZDL+S, which was not the case in ZDF+S. Salt loading decreased the expression of SGK1 in controls (ZDL+S vs ZDL 0.58±0.18 vs 1.05±0.05; p<0.05), while salt loading significantly increased the expression in diabetic rats (ZDF+S vs ZDF 1,75±0.14 vs 0.92±0.06; p<0.01). ENaC alpha expressions paralleled these findings (ZDL+S vs ZDL 0.8±0.04 vs 1.01±0.01; p<0.01; ZDF+S vs ZDF 1.57±0.17 vs 1.25±0.29). M:L of mesenteric arteries was not different between ZDF and ZDL. High salt significantly increased M:L in ZDF+S vs ZDL (10.7± 0.8 vs 6.7±0.3; p<0.01), but not in ZDL+S vs ZDL (7.2± 0.3 vs 6.1± 0.3; p=0.5). RR in this diabetes model is salt sensitive leading to marked vascular remodeling. The underlying pathophysiological mechanism may be due to inappropriate high aldosterone levels and unphysiological upregulation of SGK1 dependent sodium transporter leading to increased sodium retention.