title: Nitric oxide system is involved in glomerular hyperfiltration in Japanese normo- and micro-albuminuric patients with type 2 diabetes.
abstract: Glomerular hyperfiltration plays a pathogenic role in the early stages of diabetic nephropathy. Experimental studies in laboratory animals suggest that nitric oxide (NO) might be involved in the pathogenesis of glomerular hyperfiltration. We performed a cross-sectional study to determine the relationship between diabetic glomerular hyperfiltration and the NO system. Normoalbuminuric (n=41), microalbuminuric (n=25), and macroalbuminuric (n=16) patients with type 2 diabetes were recruited in this study and compared with age-matched 84 non-diabetic control subjects. Creatinine clearance and urinary NO(2)(-)/NO(3)(-) excretion (urinary NOx) were measured, and the expression of endothelial cell nitric oxide synthase (ecNOS) was evaluated in human renal tissues. Glomerular hyperfiltration was present in 19 (37.5%) and nine (36.6%) of normoalbuminuric and microalbuminuric type 2 diabetic patients, respectively. The urinary NOx was significantly higher in normoalbuminuric patients compared with normal subjects. Creatinine clearance correlated significantly with urinary NOx in normoalbuminuric and microalbuminuric patients. Immunohistochemical staining intensities for ecNOS were significantly increased in glomerular endothelial cells of microalbuminuric type 2 diabetic patients as compared with the control subjects. These results suggest that NO may contribute to the pathogenesis of glomerular hyperfiltration in Japanese type 2 diabetic patients.
authors.affiliation: Department of Medicine III, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hiragushi
authors.forename: H
authors.initials: H
authors.lastname: Sugimoto
authors.forename: K
authors.initials: K
authors.lastname: Shikata
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
authors.forename: N
authors.initials: N
authors.lastname: Miyatake
authors.forename: Y
authors.initials: Y
authors.lastname: Shikata
authors.forename: J
authors.initials: J
authors.lastname: Wada
authors.forename: I
authors.initials: I
authors.lastname: Kumagai
authors.forename: M
authors.initials: M
authors.lastname: Fukushima
authors.forename: H
authors.initials: H
authors.lastname: Makino
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000419:Albuminuria; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D003404:Creatinine / Q000097:blood / Q000652:urine; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D008058:Dihydrolipoamide Dehydrogenase / Q000032:analysis; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007678:Kidney Glomerulus / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000652:urine; D012016:Reference Values
chemical_list: D001786:Blood Glucose; D003404:Creatinine; D008058:Dihydrolipoamide Dehydrogenase; D006442:Glycated Hemoglobin; D009566:Nitrates; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites; C496314:NOS3 protein, human