US EPA

2835027 

Journal Article 

Significant deterioration of anti-atherogenic efficacy of nebivolol in a double (apolipoprotein E and endothelial nitric oxide synthase) knockout mouse model of atherosclerosis in comparison to single (apolipoprotein E) knockout model 

Kus, K; Wisniewska, A; Toton-Zuranska, J; Olszanecki, R; Jawien, J; Korbut, R 

2014 

Yes 

Journal of Physiology and Pharmacology
ISSN: 0867-5910
EISSN: 1899-1505 

65 

6 

877-881 

English 

25554992 

WOS:000348555200015 

Anti-atherogenic action of nebivolol in apolipoprotein E (apoE)-single knockout mouse model can be explained by its beneficial effect on endothelium, especially on endothelial nitric oxide synthase (eNOS). We, therefore, decided to use apoE and eNOS-double knockout mouse model to confirm that mechanism of nebivolol beneficial action. In apoE-single knockout mice, lesion area measured by "cross-section" of aortic roots was 79,244 ± 6,143 μm(2) in the control group versus 65,347 ± 6,152 μm(2) in nebivolol-treated group (P<0.05). However, in apoE and eNOS-double knockout mice, lesion area measured by "cross-section" of aortic roots was 92,319 ± 8,876 μm(2) in the control group versus 98,609 ± 9,164 μm(2) in nebivolol-treated group (P>0.05). The comparison between apoE-single knockout mice and apoE & eNOS-double knockout mice without treatment also showed statistically significant difference: 81,232 ± 8,264 μm(2) versus 92,319 ± 8,876 μm(2) (P<0.05). This is the first report that describes the effect of nebivolol on atherogenesis in apoE and eNOS-double knockout mice, proving directly the necessity of the presence of eNOS in endothelium for nebivolol to show its an anti-atherogenic potency. 

atherosclerosis; apolipoprotein E; double knockout mice; nebivolol; endothelial nitric oxide synthase; hypertension; beta-adrenoreceptors