Rosuvastatin improves basal nitric oxide activity of the renal vasculature in patients with hypercholesterolemia.
OBJECTIVE
Impaired endothelium-dependent vasodilation represents an early manifestation of atherosclerosis. Prospective studies have demonstrated that impaired endothelial function in the peripheral circulation of hypercholesterolemic patients predicts CV events and can be restored by statin treatment. Whether this also holds true in the renal circulation has not yet been adequately addressed.


METHODS
In a double-blind, randomized, placebo-controlled cross-over trial, 40 hypercholesterolemic patients were randomly assigned to receive rosuvastatin (10mg/day) and matching placebo. The primary objective of the study was to assess the effect of 6-week treatment with rosuvastatin on basal NOS activity of the renal vasculature, as assessed by measuring renal plasma flow (RPF) both before and after blockade of NOS with systemic infusion of N(G)-monomethyl-L-arginine (L-NMMA). In a subgroup of 20 patients we also studied the effects of a 3-day treatment regimen.


RESULTS
Compared to placebo treatment, rosuvastatin decreased LDL-cholesterol levels both after 3 days and 6 weeks of treatment. The decrease in RPF in response to L-NMMA was significantly more pronounced after 6-week therapy with rosuvastatin compared to placebo (-13.7+/-1.0% versus -11.3+/-0.7%; p=0.046), indicating increased basal NOS activity with rosuvastatin treatment. A trend towards improved basal NOS activity was already evident after 3-day treatment.


CONCLUSIONS
Treatment with rosuvastatin improved basal NOS activity in the renal circulation of hypercholesterolemic patients, suggestive of a nephroprotective effect. In view of the close relation between altered renal function and cardiovascular events, these nephroprotective effects may contribute to the improved CV prognosis associated with statin treatment.
Ott
Christian
C
Department of Nephrology and Hypertension, University of Erlangen-Nürnberg, Germany.
Schlaich
Markus P
MP
Schmidt
Bernhard M W
BM
Titze
Stephanie I
SI
Schäufele
Tim
T
Schmieder
Roland E
RE
D000293:Adolescent; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000201:enzymology; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D011743:Pyrimidines / Q000627:therapeutic use*; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use*; D013997:Time Factors; D019323:omega-N-Methylarginine / Q000097:blood / Q000494:pharmacology
D008078:Cholesterol, LDL; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D019323:omega-N-Methylarginine; D000068718:Rosuvastatin Calcium; D019001:Nitric Oxide Synthase