Premium
DDAH 2 maintains blood pressure and kidney function in response to ADMA administration in both control and diabetic rats
Author(s) -
Palm Fredrik,
Lou Zaiming,
Welch William J,
Wilcox Christopher S
Publication year - 2010
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.24.1_supplement.1059.29
Subject(s) - asymmetric dimethylarginine , medicine , endocrinology , kidney , renal function , vasoconstriction , nitric oxide , renal blood flow , diabetes mellitus , renal circulation , mean arterial pressure , blood pressure , chemistry , arginine , heart rate , biochemistry , amino acid
Asymmetric dimethylarginine (ADMA) inhibits nitric oxide synthases and is increased in diabetes. Dimethylarginine dimethylaminohydrolase (DDAH) 2 metabolizes ADMA and is expressed at different intrarenal sites, including the vasculature. We hypothesize that DDAH 2 prevents vasoconstriction and maintains kidney function in response to elevated ADMA levels. Control and diabetic rats (n=8–9/group) were injected with either vehicle or siRNA against DDAH‐2. Mean arterial blood pressure (MAP) and kidney function in response to exogenous ADMA administration were measured 48h later. siRNA reduced DDAH‐2 protein expression by −60% in both groups. MAP was only elevated in diabetic rats receiving siRNA (+10 mmHg). ADMA increased MAP in all groups compared to vehicle injected controls (+13 to 17 mmHg). Both diabetic groups had increased glomerular filtration rates (2.6±0.1 and 3.0±0.2 vs 1.6±0.2 and 1.5±0.3 ml/min/kidney; P<0.05) and ADMA reduced GFR in only the siRNA treated groups (diabetics −23% and controls −43%). Baseline renal blood flow (RBF) was decreased in both siRNA groups compared to vehicles (control 9.9±0.7 vs 7.5±0.7 and diabetes 9.8±0.9 vs 8.7±0.5 ml/min/kidney) ADMA reduced RBF in siRNA controls (−11%), vehicle diabetics (−11%) and in siRNA diabetics (−20%). DDAH‐2 protects the renal vasculature from vasoconstriction and subsequently increased MAP and reduced GFR in response to elevated ADMA levels in both control and diabetic rats. These results provide further evidence that DDAH 2 and ADMA may influence kidney function. Funding: NIH/NIDDK DK077858.