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Short-term effect of the HMG-CoA reductase inhibitor rosuvastatin on erythrocyte nitric oxide synthase activity.

Ludolph B, Bloch W, Kelm M, Schulz R, Kleinbongard P - Vasc Health Risk Manag (2007)

Bottom Line: Afterwards RBC-NOS activity and RBC deformability were determined.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Medical Clinic I, University Hospital RTWH Aachen, Germany.

ABSTRACT
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.

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Related in: MedlinePlus

Rosuvastatin increases RBC-NOS activity. RBC-NOS activity was measured by the level of eNOS protein phosphorylation and by accumulated plasma nitrite depending on rosuvastatin. (A) Phosphorylation of eNOS at Ser1177 was used to examine the phosphorylation dependent activation status of the eNOS. RBCs incubated with rosuvastatin showed a significant rise of eNOS phosphorylated at Ser1177 as compared with control. (B) Accumulated nitrite was determined in blood samples after incubation under control conditions with and without rosuvastatin. Changes in plasma nitrite reflect the sum of the release (due to NOS-dependent NO-formation) and the reuptake of nitrite by RBC.Note: *indicates significant differences from control.
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fig1: Rosuvastatin increases RBC-NOS activity. RBC-NOS activity was measured by the level of eNOS protein phosphorylation and by accumulated plasma nitrite depending on rosuvastatin. (A) Phosphorylation of eNOS at Ser1177 was used to examine the phosphorylation dependent activation status of the eNOS. RBCs incubated with rosuvastatin showed a significant rise of eNOS phosphorylated at Ser1177 as compared with control. (B) Accumulated nitrite was determined in blood samples after incubation under control conditions with and without rosuvastatin. Changes in plasma nitrite reflect the sum of the release (due to NOS-dependent NO-formation) and the reuptake of nitrite by RBC.Note: *indicates significant differences from control.

Mentions: A significantly increased phosphorylation of RBC-NOS after incubation with rosuvastatin from 3.76 ± 2.98 arbitrary units (au) to 24.88 ± 4.35 au (p < 0.02) was detected (Figure 1A). The oxidative metabolite of NO, nitrite, has been shown to reflect changes of NOS activity in vivo and in vitro (Kleinbongard et al 2003, 2006). A nitrite accumulation in plasma after incubation of whole blood with rosuvastatin from 55.8 ± 7.9 nmol/l to 98.2 ± 12.4 nmol/l (p < 0.05, Figure 1B) was detectable. Plasma nitrate levels remained unchanged. The specific NOS-inhibitor L-NMMA in addition to rosuvastatin decreased plasma nitrite levels from 64.3 ± 4.5 nmol/l to 46.6 ± 4.0 nmol/l (p < 0.01); incubation with L-NMMA alone decreased plasma nitrite levels to 43.9 ± 2.0 nmol/l (p < 0.01 to control, no significance to inhibition with rosuvastatin).


Short-term effect of the HMG-CoA reductase inhibitor rosuvastatin on erythrocyte nitric oxide synthase activity.

Ludolph B, Bloch W, Kelm M, Schulz R, Kleinbongard P - Vasc Health Risk Manag (2007)

Rosuvastatin increases RBC-NOS activity. RBC-NOS activity was measured by the level of eNOS protein phosphorylation and by accumulated plasma nitrite depending on rosuvastatin. (A) Phosphorylation of eNOS at Ser1177 was used to examine the phosphorylation dependent activation status of the eNOS. RBCs incubated with rosuvastatin showed a significant rise of eNOS phosphorylated at Ser1177 as compared with control. (B) Accumulated nitrite was determined in blood samples after incubation under control conditions with and without rosuvastatin. Changes in plasma nitrite reflect the sum of the release (due to NOS-dependent NO-formation) and the reuptake of nitrite by RBC.Note: *indicates significant differences from control.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2350149&req=5

fig1: Rosuvastatin increases RBC-NOS activity. RBC-NOS activity was measured by the level of eNOS protein phosphorylation and by accumulated plasma nitrite depending on rosuvastatin. (A) Phosphorylation of eNOS at Ser1177 was used to examine the phosphorylation dependent activation status of the eNOS. RBCs incubated with rosuvastatin showed a significant rise of eNOS phosphorylated at Ser1177 as compared with control. (B) Accumulated nitrite was determined in blood samples after incubation under control conditions with and without rosuvastatin. Changes in plasma nitrite reflect the sum of the release (due to NOS-dependent NO-formation) and the reuptake of nitrite by RBC.Note: *indicates significant differences from control.
Mentions: A significantly increased phosphorylation of RBC-NOS after incubation with rosuvastatin from 3.76 ± 2.98 arbitrary units (au) to 24.88 ± 4.35 au (p < 0.02) was detected (Figure 1A). The oxidative metabolite of NO, nitrite, has been shown to reflect changes of NOS activity in vivo and in vitro (Kleinbongard et al 2003, 2006). A nitrite accumulation in plasma after incubation of whole blood with rosuvastatin from 55.8 ± 7.9 nmol/l to 98.2 ± 12.4 nmol/l (p < 0.05, Figure 1B) was detectable. Plasma nitrate levels remained unchanged. The specific NOS-inhibitor L-NMMA in addition to rosuvastatin decreased plasma nitrite levels from 64.3 ± 4.5 nmol/l to 46.6 ± 4.0 nmol/l (p < 0.01); incubation with L-NMMA alone decreased plasma nitrite levels to 43.9 ± 2.0 nmol/l (p < 0.01 to control, no significance to inhibition with rosuvastatin).

Bottom Line: Afterwards RBC-NOS activity and RBC deformability were determined.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Medical Clinic I, University Hospital RTWH Aachen, Germany.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus