title: Endothelial dysfunction and reduced nitric oxide in resistance arteries in autosomal-dominant polycystic kidney disease.
abstract: BACKGROUND
  Patients with autosomal-dominant polycystic kidney disease (ADPKD) have defective endothelium-dependent relaxation (EDR). We investigated the relationship between endothelial dysfunction and nitric oxide generation in hypertension and chronic renal insufficiency (CRI) in ADPKD.
  
  
  METHODS
  We contrasted acetylcholine (ACh)-induced EDR, 3-morphollinosydnonimine (SIN-1)-induced endothelium-independent relaxation (EIDR) and constitutive nitric oxide synthase (cNOS) activity in subcutaneous resistance vessels and plasma levels and excretion of NO2-/NO3- (NOX) in normal, control (N = 10) patients with ADPKD or essential hypertension.
  
  
  RESULTS
  EDR was decreased significantly in normotensive ADPKD (N = 9), but more severely in hypertensive ADPKD (N = 6), or those with CRI (N = 5) and in essential hypertension (N = 9). The increases in EDR with l-arginine and decreases with LG-nitro-l-arginine methyl ester (L-NAME) were lost in all groups of patients with ADPKD and in essential hypertension except for a modest effect of L-NAME in normotensive ADPKD. EIDR was unimpaired throughout. Vascular cNOS activity and renal NOX excretion were reduced profoundly in patients with all categories of ADPKD and especially in those with hypertension.
  
  
  CONCLUSIONS
  EDR in resistance vessels from patients with ADPKD is impaired even in the absence of hypertension or CRI, but becomes more marked as hypertension develops. Patients with ADPKD have defective nitric oxide generation from diminished cNOS activity. Endothelial dysfunction and impaired cNOS activity in ADPKD may predispose to hypertension whose occurrence is accompanied by a further sharp deterioration in EDR.
authors.affiliation: Department of Nephrology, Herlev Hospital, University of Copenhagen, Herlev, Denmark. dw32@georgetown.edu
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Jens
authors.initials: J
authors.lastname: Iversen
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Wilcox
authors.forename: Svend
authors.initials: S
authors.lastname: Strandgaard
mesh_terms: D000328:Adult; D001120:Arginine / Q000494:pharmacology; D001158:Arteries / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000209:etiology; D008297:Male; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000097:blood / Q000652:urine; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000097:blood / Q000652:urine; D016891:Polycystic Kidney, Autosomal Dominant / Q000150:complications / Q000378:metabolism / Q000503:physiopathology* / Q000652:urine; D014655:Vascular Resistance; D014664:Vasodilation
chemical_list: D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D001120:Arginine; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D019331:NG-Nitroarginine Methyl Ester