Short-term effect of the HMG-CoA reductase inhibitor rosuvastatin on erythrocyte nitric oxide synthase activity.
Prevention and treatment of cardiovascular disorders by HMG-CoA reductase inhibitors (or statins), beyond their lipid-lowering properties, have been demonstrated including activation of the endothelial nitric oxide synthase (eNOS). Beside endothelial cells, red blood cells (RBCs) possess NOS and produce nitric oxide (NO), which contributes to RBC deformability. The present study tested the capacity of statins to activate NOS in RBCs and subsequently to modulate RBC deformability in vitro. Blood samples of healthy young volunteers were incubated with or without rosuvastatin. Afterwards RBC-NOS activity and RBC deformability were determined. Rosuvastatin incubation significantly increased NOS phosphorylation, NOS dependent NO-formation, and RBC deformability. The NOS inhibitor NG- monomethyl-L-arginine reversed the stimulatory effect of rosuvastatin on RBC-NOS activity. This NO dependent effect of rosuvastatin might have an important influence on microcirculation and may offer new perspectives for the therapeutic use of statins.
Ludolph
Barbara
B
Department of Medicine, Medical Clinic I, University Hospital RTWH Aachen, Germany.
Bloch
Wilhelm
W
Kelm
Malte
M
Schulz
Rainer
R
Kleinbongard
Petra
P
D004791:Enzyme Inhibitors / Q000494:pharmacology; D004907:Erythrocyte Deformability / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D005464:Fluorobenzenes / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D010766:Phosphorylation / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009573:Nitrites; D011743:Pyrimidines; D013449:Sulfonamides; D019323:omega-N-Methylarginine; D000068718:Rosuvastatin Calcium; D019001:Nitric Oxide Synthase