Abstract
This study was designed to test whether altered aldosterone-related sodium handling leads to salt-sensitive blood pressure in diabetes and thus may exaggerate end-organ damage. Zucker diabetic fatty (ZDF) rats, a model of type 2 diabetes, and Zucker lean (ZL) rats, as euglycemic controls, were divided into groups receiving normal (0.28%) (ZDF+N, ZL+N) and high-salt (5.5%) diets (ZDF+S, ZL+S) for ...
Abstract
This study was designed to test whether altered aldosterone-related sodium handling leads to salt-sensitive blood pressure in diabetes and thus may exaggerate end-organ damage. Zucker diabetic fatty (ZDF) rats, a model of type 2 diabetes, and Zucker lean (ZL) rats, as euglycemic controls, were divided into groups receiving normal (0.28%) (ZDF+N, ZL+N) and high-salt (5.5%) diets (ZDF+S, ZL+S) for 10 weeks. Renal mRNA expression of serum-and glucocorticoid-inducible kinase 1 (SGK1) and sodium transporters (for example, the epithelial sodium channel-alpha, ENaC alpha) were measured by quantitative reverse transcriptase-PCR. Vascular hypertrophy (media-to-lumen ratio, M/L) in mesenteric resistance arteries was assessed using a pressurized myograph. Systolic blood pressure (SBP) was significantly higher in ZDF+S vs. ZDF+N (146 +/- 2 vs. 133 +/- 3 mm Hg; P < 0.05), whereas there was no difference between ZL+S and ZL+N (151 +/- 3 vs. 147 +/- 3 mm Hg). Plasma sodium concentration was higher in ZDF+S vs. ZDF+N, whereas there was no difference between ZL+S and ZL+N. Plasma aldosterone concentration (PAC) was higher in ZDF+N as compared with ZL+N (191 +/- 23 vs. 95 +/- 35 pg ml(-1); P<0.05). PAC decreased to zero in ZL+S, which was not the case in ZDF+S (0 +/- 0 vs. 37 +/- 2 pg ml(-1)). Salt loading decreased the mRNA expression of SGK1 in euglycemic controls (ZL+S 0.58 +/- 0.2 vs. ZL+N 1.05 +/- 0.05; P 0.05), whereas it significantly increased SGK1 expression in diabetic rats (ZDF+S 1.75 +/- 0.15 vs. ZDF+N 0.92 +/- 0.07; P<0.01). ENaCa mRNA expression paralleled these changes. The M/L of mesenteric resistance arteries was not different between ZDF+N and ZL+N. High salt significantly increased the M/L in ZDF+S vs. ZDF+N, but not in ZL+S vs. ZL+N. Systolic blood pressure in this model of type 2 diabetes mellitus is salt sensitive, leading to marked vascular remodeling. The underlying pathophysiological mechanism may be inappropriately high levels of aldosterone and up-regulation of SGK1-dependent renal sodium transport by ENaCa, leading to net increased sodium retention. Hypertension Research (2010) 33, 1082-1088; doi:10.1038/hr.2010.132; published online 22 July 2010
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