title: Hyperaldosteronism and altered expression of an SGK1-dependent sodium transporter in ZDF rats leads to salt dependence of blood pressure.
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-α, ENaCα) 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). ENaCα 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 ENaCα, leading to net increased sodium retention.
authors.affiliation: Department of Internal Medicine II, University Medical Center Regensburg, Franz Josef Strauss Allee 11, Regensburg, Germany. Markus.Resch@klinik.uni-regensburg.de
authors.forename: Markus
authors.initials: M
authors.lastname: Resch
authors.forename: Tobias
authors.initials: T
authors.lastname: Bergler
authors.forename: Sabine
authors.initials: S
authors.lastname: Fredersdorf
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Griese
authors.forename: Joachim
authors.initials: J
authors.lastname: Weil
authors.forename: Peter
authors.initials: P
authors.lastname: Kreuzer
authors.forename: Sabine
authors.initials: S
authors.lastname: Brunner
authors.forename: Günter A J
authors.initials: GA
authors.lastname: Riegger
authors.forename: Andreas
authors.initials: A
authors.lastname: Luchner
authors.forename: Dierk H
authors.initials: DH
authors.lastname: Endemann
mesh_terms: D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology*; D004195:Disease Models, Animal; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D006929:Hyperaldosteronism / Q000378:metabolism / Q000503:physiopathology*; D017874:Immediate-Early Proteins / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D012964:Sodium / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D000450:Aldosterone; D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D012964:Sodium; D017673:Sodium Chloride, Dietary; D000099184:Serum-Glucocorticoid Regulated Kinases