P94	Rosuvastatin activates an erythrocyte eNOS: Effects on NO-formation and erythrocyte deformability.
1B.Ludolph, 1P.Kleinbongard, 1I.Kumara, 1K.Lysaja, 1M.Kelm, 2R.Schulz
1Department of Medicine, Division of Cardiology, Pulmonary Diseases and Angiology, Heinrich-Heine-University, Düsseldorf, DE; 2Institute of Pathophysiology, Medical School, University of Essen, Essen, DE.

Background: Atheroprotective effects of HMG-CoA reductase inhibitors (or statins), independent of their lipid-lowering properties, had been demonstrated. One of these effects refers to their ability to activate endothelial nitric oxide synthase (eNOS). Beside endothelial cells, red blood cells (RBC) also possess eNOS and produce nitric oxide (NO) thereby contributing to RBC deformability and regulation of vascular tone. The present study now tested the capacity of statins to 1) activate eNOS in RBCs and 2) to modulate RBC deformability. Methods: Blood samples of healthy young volunteers were incubated with and without 20 ng/ml rosuvastatin, the plasma concentration achieved in humans during standard therapy, at 37°C for 30 minutes. NO production was measured indirectly through its N-oxides nitrite and nitrate using chemiluminescence and flow injection analysis. RBC deformability was examined with pure erythrocytes adjusted to a hematocrite of 35% through a modified filtration method according to Reid et al (1976). Results: Rosuvastatin increased nitrite levels in plasma from 89.6±9.9 nmol/l to 147.7±7.7 nmol/l (n=6, p<0,01). Nitrate levels in plasma remained almost unchanged (19.04±1.11 µmol/l vs. 19.56±1.02). RBC deformability increased after incubation with rosuvastatin from 2.00±0.35 ml/min (controls) to 2,56±0,37 ml/min (n=6, p<0,05). Conclusions: Rosuvastatin activates eNOS in RBCs, increases NO formation and subsequently increases RBC deformability. This pleiotropic effect might have an important influence on microcirculation and may offer interesting new perspectives to the therapeutic use of statins.

Copyright © 2005 S. Karger AG, Basel. Any further use of this abstract requires written permission from the publisher.