title: Effect of atorvastatin on renal NO availability and tubular function in patients with stage II-III chronic kidney disease and type 2 diabetes.
abstract: BACKGROUND
  Statins have beneficial effects on cardiovascular morbidity and mortality independently of reduction of plasma cholesterol.
  
  
  OBJECTIVE
  In patients with type 2 diabetes and nephropathy, chronic kidney disease stage II-III, we tested the hypothesis that atorvastatin increased systemic and renal nitric oxide (NO) availability using L-NMMA as an inhibitor of NO production. We performed a randomized, placebo-controlled, crossover study, using atorvastatin/placebo treatment for five days with a standardized diet and fluid intake. We measured brachial BP (bBP), central BP (cBP), GFR, urinary output (OU), free water clearance (CH2O), fractional excretion of sodium (FENa), urinary excretion of albumin (UAER and UACR), AQP2 (u-AQP2) and ENaC (u-ENaCγ) and plasma concentrations of vasoactive hormones: renin, angiotensin II, aldosterone, arginine vasopressin, endothelin-1 and brain natriuretic peptide.
  
  
  RESULTS
  During atorvastatin and placebo treatment, L-NMMA infusion, changed the effect variables significantly, but to the same extent, i.e. an increase in bBP and cBP, and a decrease in GFR, OU, CH2O, FENa, u-AQP2 and u-ENaCγ. In addition, renin and angiotensin II was reduced, aldosterone increased, and vasopressin, endothelin-1 and brain natriuretic hormone unchanged.
  
  
  CONCLUSIONS
  During, atorvastatin and placebo treatment, inhibition of nitric oxide synthesis induced the same response in brachial and central blood pressure, GFR, renal tubular function and vasoactive hormones. Thus, atorvastatin did not change nitric oxide availability in type 2 diabetics with nephropathy.
authors.affiliation: University Clinic in Nephrology and Hypertension, Department of Medical Research and University of Aarhus.
authors.forename: Frank H
authors.initials: FH
authors.lastname: Mose
authors.forename: Thomas
authors.initials: T
authors.lastname: Larsen
authors.forename: Janni M
authors.initials: JM
authors.lastname: Jensen
authors.forename: Annebirthe B
authors.initials: AB
authors.lastname: Hansen
authors.forename: Jesper N
authors.initials: JN
authors.lastname: Bech
authors.forename: Erling B
authors.initials: EB
authors.lastname: Pedersen
mesh_terms: D000368:Aged; D001127:Arginine Vasopressin / Q000097:blood; D000069059:Atorvastatin; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D063177:Pulse Wave Analysis; D011758:Pyrroles / Q000494:pharmacology*; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016896:Treatment Outcome; D059289:Vascular Stiffness; D014667:Vasopressins / Q000097:blood; D019323:omega-N-Methylarginine / Q000627:therapeutic use
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D014667:Vasopressins; D001127:Arginine Vasopressin; D020097:Natriuretic Peptide, Brain; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D000069059:Atorvastatin