Hypercholesterolaemia and treatment with statins do not alter L-arginine-induced changes of renal haemodynamics.
BACKGROUND
Hypercholesterolaemia has been found to impair endothelial function in the systemic and coronary circulations and lipid-lowering therapy with statins has been shown to improve this abnormality.


METHODS
We examined the impact of hypercholesterolaemia on L-arginine-induced renal vascular relaxation by a cross-sectional study, and the effects of lipid-lowering therapy by a double-blind, randomized, placebo-controlled study. Using constant infusion input clearance technique (PAH and inulin respectively), changes of renal plasma flow (RPF) and glomerular filtration rate (GFR) in response to intravenous infusions of L-arginine (100 mg/kg/30 min and 500 mg/kg/30 min) were studied in 21 hypercholesterolaemic humans (age 57+/-9 years, LDL-cholesterol 211+/-35 mg/dl) and in 20 young healthy (age 26+/-2 years, LDL-cholesterol 90+/-27 mg/dl) and 20 older healthy age-matched control individuals (age 50+/-8 years, LDL-cholesterol 106+/-20 mg/dl). In addition, changes of blood pressure, heart rate, urinary excretion of sodium, and cyclic guanosine monophosphate were measured. Patients were analysed before and after 3 months treatment with either fluvastatin (40 mg twice daily, n=11) or placebo (n=10).


RESULTS
In hypercholesterolaemic patients, L-arginine increased RPF and GFR (P<0.01) and urinary excretion of sodium (P<0.05) in a dose-dependent manner. Interestingly, changes were similar between the hypercholesterolaemic patients and the young and the age-matched control individuals (DeltaRPF 100 mg/kg/30 min, 40+/-51 ml/min vs 40+/-52 ml/min, P=NS; DeltaRPF 500 mg/kg/30 min, 114+/-85 ml/min vs 130+/-78 ml/min, P=NS). L-arginine significantly lowered systemic arterial pressure and increased heart rate in all groups. Despite significant reductions in LDL-cholesterol levels (291+/-35 mg/dl vs 213+/-30 mg/dl, P<0.001), treatment with fluvastatin did not alter the renal haemodynamic response pattern to L-arginine infusion when compared to baseline values and to those with placebo.


CONCLUSIONS
In contrast to studies performed in the vasculature of the human forearm or the coronary circulation, our results suggest that hypercholesterolaemia is not associated with an impaired L-arginine-induced renal vascular relaxation.
Fleischmann
Erwin H
EH
Department of Medicine IV/4/Nephrology, University of Erlangen-Nürnberg, Germany.
Schlaich
Markus P
MP
Schmidt
Bernhard M W
BM
Oehmer
Sebastian
S
Schmieder
Roland E
RE
D000368:Aged; D001120:Arginine / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D015331:Cohort Studies; D006152:Cyclic GMP / Q000652:urine; D004311:Double-Blind Method; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000503:physiopathology*; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D009994:Osmolar Concentration; D012079:Renal Circulation / Q000187:drug effects*; D014664:Vasodilation; D014665:Vasodilator Agents / Q000097:blood / Q000494:pharmacology*
D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D014665:Vasodilator Agents; D000077340:Fluvastatin; D001120:Arginine; D006152:Cyclic GMP