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Published on: November 10, 2017
Hypercholesterolaemia and treatment with statins do not alter L-arginine-induced changes of renal haemodynamics
Erwin H Fleischmann1, Markus P Schlaich, Bernhard M W Schmidt
1Department of Medicine IV/4/Nephrology, University of Erlangen-Nürnberg, Germany.
Insights
High cholesterol (hypercholesterolaemia) does not impair L-arginine-induced renal vascular relaxation, contrary to findings in other blood vessels. Lipid-lowering therapy with fluvastatin also did not alter this renal response.
Area of Science:
- Nephrology
- Cardiovascular Physiology
- Endocrinology
Background:
- Hypercholesterolaemia impairs endothelial function in systemic and coronary circulations.
- Lipid-lowering therapy, particularly with statins, can improve endothelial dysfunction.
Purpose of the Study:
- To investigate the impact of hypercholesterolaemia on L-arginine-induced renal vascular relaxation.
- To evaluate the effects of lipid-lowering therapy on renal vascular response to L-arginine.
Main Methods:
- Cross-sectional and double-blind, randomized, placebo-controlled studies were conducted.
- Renal plasma flow (RPF) and glomerular filtration rate (GFR) responses to L-arginine infusions were measured in hypercholesterolaemic and healthy individuals.
- Patients received fluvastatin or placebo for 3 months, with renal haemodynamics assessed before and after treatment.
Main Results:
- Hypercholesterolaemia did not impair L-arginine-induced increases in RPF and GFR compared to healthy controls.
- L-arginine dose-dependently increased RPF and GFR, lowered blood pressure, and increased heart rate in all groups.
- Fluvastatin treatment significantly reduced LDL-cholesterol but did not alter the renal haemodynamic response to L-arginine.
Conclusions:
- Hypercholesterolaemia is not associated with impaired L-arginine-induced renal vascular relaxation.
- Renal vascular response to L-arginine appears preserved in hypercholesterolaemia, unlike in other vascular beds.
- Lipid-lowering therapy did not modify the renal vascular response to L-arginine in this study.
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.
Conclusion:
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.
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