In:
Journal of Vascular Research, S. Karger AG, Vol. 49, No. 5 ( 2012), p. 432-440
Abstract:
〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Impaired vascular compliance is associated with cardiovascular mortality. The effects of heart rate on vascular compliance are unclear. Therefore, we characterized effects of heart rate reduction (HRR) by I( 〈 i 〉 f 〈 /i 〉 ) current inhibition on aortic compliance and underlying molecular mechanisms in apolipoprotein E-deficient (ApoE 〈 sup 〉 – 〈 /sup 〉 / 〈 sup 〉 – 〈 /sup 〉 ) mice. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 ApoE 〈 sup 〉 – 〈 /sup 〉 / 〈 sup 〉 – 〈 /sup 〉 mice fed a high-cholesterol diet and wild-type (WT) mice were treated with ivabradine (20 mg/kg/d) or vehicle for 6 weeks. Compliance of the ascending aorta was evaluated by MRI. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Ivabradine reduced heart rate by 113 ± 31 bpm (∼19%) in WT mice and by 133 ± 6 bpm (∼23%) in ApoE 〈 sup 〉 – 〈 /sup 〉 / 〈 sup 〉 – 〈 /sup 〉 mice. Compared to WT controls, ApoE 〈 sup 〉 – 〈 /sup 〉 / 〈 sup 〉 – 〈 /sup 〉 mice exhibited reduced distensibility and circumferential strain. HRR by ivabradine increased distensibility and circumferential strain in ApoE 〈 sup 〉 – 〈 /sup 〉 / 〈 sup 〉 – 〈 /sup 〉 mice but did not affect both parameters in WT mice. Ivabradine reduced aortic protein and mRNA expression of the angiotensin II type 1 (AT1) receptor and reduced rac1-GTPase activity in ApoE 〈 sup 〉 – 〈 /sup 〉 / 〈 sup 〉 – 〈 /sup 〉 mice. Moreover, membrane translocation of p47 〈 sup 〉 phox 〈 /sup 〉 was inhibited. In ApoE 〈 sup 〉 – 〈 /sup 〉 / 〈 sup 〉 – 〈 /sup 〉 mice, HRR induced anti-inflammatory effects by reduction of aortic mRNA expression of IL-6, TNF-alpha and TGF-beta. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 HRR by ivabradine improves vascular compliance in ApoE 〈 sup 〉 – 〈 /sup 〉 / 〈 sup 〉 – 〈 /sup 〉 mice. Contributing mechanisms include downregulation of the AT1 receptor, attenuation of oxidative stress and modulation of inflammatory cytokine expression.
Type of Medium:
Online Resource
ISSN:
1018-1172
,
1423-0135
Language:
English
Publisher:
S. Karger AG
Publication Date:
2012
detail.hit.zdb_id:
1482726-8
