Premium
Increased Renal Oxidative Stress in hGRK4 486V Transgenic Mice
Author(s) -
Diao Zhenyu,
Armando Ines,
Asico Laureano,
Cuevas Santiago,
Jose Pedro,
wang xiaoyan
Publication year - 2015
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.29.1_supplement.811.25
Subject(s) - oxidative stress , medicine , endocrinology , genetically modified mouse , chemistry , kidney , reactive oxygen species , transgene , biology , biochemistry , gene
Variants of hGRK4 are associated with human essential hypertension. hGRK4 486V transgenic mice have salt‐sensitive hypertension. Because renal oxidative stress is increased in some rodent models of salt‐sensitive hypertension, we quantified renal expression of reactive oxygen species‐related proteins of hGRK4 486V transgenic and non‐transgenic (NT) mice on normal (NS, 0 . 8% ) and high (HS, 4%) NaCl diets . Systolic blood pressure was similar in hGRK4 486V (89.83±2.7, mm Hg, n=9) and NT (94.7±2.5) mice on NS diet and elevated in hGRK4 486V (114±6.1) but not in NT mice (94.1±2.8) on HS diet. The renal expressions of NOX1, 2, and 4, were similar in both strains on NS diet but NOX2 was decreased by HS in NT (28±7, % of NT on NS diet, n=5‐6/group). On NS diet, CuZnSOD and ECSOD were similar in the two mouse strains while MnSOD (66±3%) was lower in GRK4 486V than NT mice. However, on HS diet, CuZnSOD (87±7%), MnSOD (70±3%), and ECSOD (55±7%) were decreased in GRK4 486V mice not in NT mice. HO‐2, not HO‐1, was slightly greater in GRK4 486V than NT mice on NS diet (117±7%) but this difference was abolished by HS diet. Urinary 8‐isoprostane was lower in GRK4 486V than NT mice (57±2.5 vs 70±0.1, ng/mg of Cr) on NS diet but increased to a greater extent in GRK4 486V than NT mice (197±18 vs128±6) on HS diet. Renal SOD activity and superoxide production were similar in both strains on NS diet. HS diet decreased SOD activity (81.6±2.7%) and increased superoxide (138.9±6.6%) production in GRK4 486V but not in NT mice. HS diet also decreased the renal expression of NOS3, not NOS 1 and 2, in GRK4 486V (49±2%) but not in NT mice. These findings suggest that the salt‐sensitive hypertension of GRK4 486V mice is related to renal oxidative stress due to decreased protein expression and activity of SODs and decreased NOS3 protein.