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Serum and glucocorticoid‐regulated kinase mediates hypertension and end organ damage in DOCA‐salt hypertension
Author(s) -
Schnackenberg Christine G.,
Costell Melissa H.,
Hoang Bao,
Duddy Graham,
Willette Robert N.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.969.14
Subject(s) - sgk1 , medicine , endocrinology , blood pressure , reabsorption , natriuresis , renal sodium reabsorption , renal function , kidney , pathophysiology of hypertension , left ventricular hypertrophy , epithelial sodium channel , mineralocorticoid receptor , glucocorticoid , sodium , chemistry , aldosterone , organic chemistry
Serum and glucocorticoid‐regulated kinase 1 (SGK1) plays an important role in mediating mineralocorticoid receptor stimulated sodium reabsorption. We have previously shown that SGK2 can compensate for renal sodium reabsorption in the absence of SGK1. Therefore, we tested the hypothesis that SGK1 and SGK2 contribute to the hypertension and end organ damage during DOCA‐salt hypertension. The systolic blood pressure, cardiac, and renal responses to DOCA‐salt hypertension or SHAM were determined in sgk1 −/− , sgk2 −/− double knockout (DKO, n = 20) and homozygous wildtype littermates (WT, n = 19). During baseline conditions DKO had lower body weight and systolic blood pressure, and higher water intake and heart rate compared to WT. After 11 weeks of DOCA‐salt hypertension, genetic ablation of SGK1 and SGK2 significantly attenuated the hypertension (192 ± 8 vs. 158 ± 6 mmHg), microalbuminuria (9.9 ± 2.1 vs. 5.0 ± 1.7 mg/day), left ventricular hypertophy, renal fibrosis, protein deposition, and glomerular hypertrophy (3.3 ± 0.2 vs. 1.7 ± 0.3 total renal score), and morbidity and mortality (6/11 vs. 1/9 deaths). Absence of functional SGK1 and SGK2 shifted the pressure‐natriuresis curve to the left and increased the slope, indicating improved renal function and reduced salt‐sensitivity. These results suggest that SGK1 and SGK2 contribute to the cardiovascular and renal pathophysiology of DOCA‐salt hypertension.