Impaired basal NO activity in patients with glomerular disease and the influence of oxidative stress.
Endothelial dysfunction has been found to be linked to and predictive of cardiovascular events. Whether endothelial function of the renal vasculature is impaired in patients with chronic glomerular disease and whether oxidative stress is of importance in this setting has not yet been determined. In this study, endothelial function of the renal vasculature was investigated in 25 patients with chronic glomerular disease and 50 control subjects matched for age and blood pressure. Renal plasma flow (RPF) and glomerular filtration rate were measured by constant infusion input clearance technique at baseline and following infusions of the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 4.25 mg/kg), the substrate of NOS L-arginine (100 mg/kg) and the antioxidant vitamin C (3 g co-infused with L-arginine 100 mg/kg). At baseline, RPF was similar in the two groups. The reduction in RPF in response to L-NMMA was less pronounced in patients with chronic glomerular disease compared to control subjects (-4.6+/-12 vs -9.8+/-9%; P=0.040), indicating reduced basal nitric oxide (NO) activity in chronic glomerular disease. Co-infusion of the antioxidant vitamin C on top of L-arginine induced a more pronounced increase in RPF in patients with chronic glomerular disease than in control subjects (21.7+/-17 vs 10.9+/-22%; P=0.036). Our findings suggest that basal NO activity of the renal vasculature is reduced in patients with chronic glomerular disease compared to age- and blood pressure-matched control subjects. This might be in part related to increased oxidative stress.
Schäufele
T G
TG
Department of Medicine 4/Nephrology and Hypertension, University of Erlangen-Nürnberg, Erlangen, Germany.
Schlaich
M P
MP
Delles
C
C
Klingbeil
A U
AU
Fleischmann
E H
EH
Schmieder
R E
RE
D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology; D016022:Case-Control Studies; D002908:Chronic Disease; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D005215:Fasting; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005921:Glomerulonephritis / Q000201:enzymology* / Q000378:metabolism; D006339:Heart Rate / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage* / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D018384:Oxidative Stress; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000975:Antioxidants; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; D001205:Ascorbic Acid; D019331:NG-Nitroarginine Methyl Ester