Document Detail


Hyperaldosteronism and altered expression of an SGK1-dependent sodium transporter in ZDF rats leads to salt dependence of blood pressure.
MedLine Citation:
PMID:  20664544     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Markus Resch; Tobias Bergler; Sabine Fredersdorf; Daniel P Griese; Joachim Weil; Peter Kreuzer; Sabine Brunner; Günter A J Riegger; Andreas Luchner; Dierk H Endemann
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-22
Journal Detail:
Title:  Hypertension research : official journal of the Japanese Society of Hypertension     Volume:  33     ISSN:  1348-4214     ISO Abbreviation:  Hypertens. Res.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-05     Completed Date:  2011-02-01     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  9307690     Medline TA:  Hypertens Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  1082-8     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine II, University Medical Center Regensburg, Franz Josef Strauss Allee 11, Regensburg, Germany. Markus.Resch@klinik.uni-regensburg.de
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MeSH Terms
Descriptor/Qualifier:
Aldosterone / metabolism
Animals
Blood Pressure / drug effects*,  physiology
Diabetes Mellitus, Type 2 / metabolism*,  physiopathology*
Disease Models, Animal
Epithelial Sodium Channel / metabolism*
Hyperaldosteronism / metabolism,  physiopathology*
Immediate-Early Proteins / metabolism*
Kidney / metabolism
Male
Mesenteric Arteries / drug effects,  physiopathology
Protein-Serine-Threonine Kinases / metabolism*
Rats
Rats, Zucker
Sodium / metabolism
Sodium Chloride, Dietary / pharmacology*
Vascular Resistance / drug effects,  physiology
Chemical
Reg. No./Substance:
0/Epithelial Sodium Channel; 0/Immediate-Early Proteins; 0/Sodium Chloride, Dietary; 52-39-1/Aldosterone; 7440-23-5/Sodium; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/serum-glucocorticoid regulated kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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