Reference : Rosuvastatin decreases caveolin-1 and improves nitric oxide-dependent heart rate and blo...
Scientific journals : Article
Human health sciences : Anesthesia & intensive care
http://hdl.handle.net/2268/110549
Rosuvastatin decreases caveolin-1 and improves nitric oxide-dependent heart rate and blood pressure variability in apolipoprotein E-/- mice in vivo.
English
Pelat, Michel [> > > >]
Dessy, Chantal [> > > >]
MASSION, Paul mailto [Centre Hospitalier Universitaire de Liège - CHU > > Soins intensifs]
Desager, Jean-Pierre [> > > >]
Feron, Olivier [> > > >]
Balligand, Jean-Luc [> > > >]
2003
Circulation
Lippincott Williams & Wilkins
107
19
2480-6
Yes (verified by ORBi)
0009-7322
1524-4539
Hagerstown
MD
[en] Animals ; Aorta/drug effects/metabolism ; Apolipoproteins E/deficiency/genetics ; Autonomic Nervous System/physiopathology ; Blood Pressure/drug effects ; Blood Pressure Monitoring, Ambulatory ; Caveolin 1 ; Caveolins/metabolism ; Cholesterol/blood ; Chronobiology Disorders/complications/drug therapy/physiopathology ; Electrocardiography, Ambulatory ; Fluorobenzenes/pharmacology ; Heart Rate/drug effects ; Hyperlipidemias/complications/drug therapy/physiopathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myocardium/metabolism ; Nitric Oxide/metabolism ; Nitric Oxide Synthase/metabolism ; Nitric Oxide Synthase Type II ; Nitric Oxide Synthase Type III ; Pyrimidines ; Sulfonamides ; Treatment Outcome
[en] BACKGROUND: Decreased heart rate variability (HRV) and increased blood pressure variability (BPV), determined in part by nitric oxide (NO)-dependent endothelial dysfunction, are correlated with adverse prognosis in cardiovascular diseases. We examined potential alterations in BPV and HRV in genetically dyslipidemic, apolipoprotein (apo) E-/-, and control mice and the effect of chronic statin treatment on these parameters in relation to their NO synthase (NOS)-modifying properties. METHODS AND RESULTS: BP and HR were recorded in unrestrained, nonanesthetized mice with implanted telemetry devices with or without rosuvastatin. Cardiac and aortic expression of endothelial NOS and caveolin-1 were measured by immunoblotting. Both systolic BP and HR were elevated in apoE-/- mice, with abolition of their circadian cycles. Spectral analysis showed an increase in their systolic BPV in the very-low-frequency (+17%) band and a decrease in HRV in the high-frequency (-57%) band, reflecting neurohumoral and autonomic dysfunction. Decreased sensitivity to acute injection of atropine or an NOS inhibitor indicated basal alterations in both parasympathetic and NOS regulatory systems in apoE-/- mice. Aortic caveolin-1 protein, an inhibitor of endothelial NOS, was also increased in these mice by 2.0-fold and correlated positively with systolic BPV in the very-low-frequency band. Rosuvastatin treatment corrected the hemodynamic and caveolin-1 expression changes despite persisting elevated plasma cholesterol levels. CONCLUSIONS: Rosuvastatin decreases caveolin-1 expression and promotes NOS function in apoE-/-, dyslipidemic mice in vivo, with concurrent improvements in BPV and HRV. This highlights the beneficial effects of rosuvastatin on cardiovascular function beyond those attributed to lipid lowering.
http://hdl.handle.net/2268/110549
10.1161/01.CIR.0000065601.83526.3E

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