GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Abstract 477: Selective Heart Rate Reduction Via Inhibition Of The I F -current Prevents Atherosclerosis And Improves Endothelial And Erectile Function In Apoe −/− Mice
    Ovid Technologies (Wolters Kluwer Health) ; 2007
    In:  Circulation Vol. 116, No. suppl_16 ( 2007-10-16)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 116, No. suppl_16 ( 2007-10-16)
    Abstract: Introduction : Elevated resting heart rate (HR) is associated with increased risk for cardiovascular morbidity and mortality. Erectile dysfunction is associated with endothelial dysfunction and atherosclerosis due to similar risk factors. We hypothesized that HR reduction may influence endothelial- and erectile function and tested the effects of the I f -current inhibitor ivabradine in ApoE−/− mice. Methods and Results: Male ApoE−/− mice fed a high-cholesterol diet were treated with ivabradine (iva) (10 mg/kg/d p.o.) or vehicle (n=10 per group) for 6 weeks. Treatment with ivabradine reduced HR by 13.4% (iva 472±9 bpm vs vehicle 545±11 bpm, p 〈 0.01). High cholesterol feeding led to severe atherosclerosis in the aortic sinus and the aorta. Ivabradine reduced atherosclerotic plaque size in the aortic root from 32±4% to 18±2% and in the ascending aorta from 26±4% to 7±1% (p 〈 0,05). Endothelium dependent relaxation of aortic rings and corpora cavernosa to carbachol was significantly improved in ivabradine fed ApoE−/− mice compared to controls (p 〈 0.01). Aortic eNOS mRNA expression, quantified by real time PCR with the TaqMan system was upregulated to 156±11% (p 〈 0.05) in aortic rings after treatment with ivabradine. HR reduction led to attenuation of NADPH oxidase activity to 48±6% as measured by a lucigenin-enhanced chemiluminescence assay and decreased L-012 chemiluminescence to 24±9% (both p 〈 0.05). Lipidperoxidation was reduced to 65±8% in the vasculature of the iva group compared to vehicle treatment (p 〈 0.05). DHE fluorescence microscopy in aortic sections detected reduction of ROS release to 62±4% in ivabradine treated mice (p 〈 0.01). Conclusions : Selective HR reduction improves endothelial as well as erectile function and reduces atherosclerotic plaque formation in ApoE−/− mice. Those functional effects are mediated by decreased oxidative stress and upregulation of endothelial NOS (eNOS). These results identify HR as a risk factor for vascular disease and support the importance of heart rate reduction in vascular prevention.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.116.suppl_16.II_81-a
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2007
    detail.hit.zdb_id: 1466401-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Abstract 1738: The I( f )-inhibitor Ivabradine Exerts Vascular Anti-oxidative And Anti-inflammatory Effects Selectively Mediated By Reduction Of Heart Rate
    Ovid Technologies (Wolters Kluwer Health) ; 2008
    In:  Circulation Vol. 118, No. suppl_18 ( 2008-10-28)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 118, No. suppl_18 ( 2008-10-28)
    Abstract: Objective: In epidemiological studies, elevated resting heart rate (HR) is associated with increased cardiovascular morbidity. We therefore characterized the effects of selective heart rate reduction by inhibition of the I (f) -current by ivabradine (IVA) in mice. Methods and Results: Male ApoE −/− mice fed a high-cholesterol diet were treated with IVA (10 mg/kg/d) or vehicle for 6 weeks (n = 10 per group). IVA reduced HR by 13.4% (472 ± 9 vs 545 ± 11 bpm, p 〈 0.01) but did not alter blood pressure or lipid levels. Endothelium dependent relaxation of aortic rings was significantly improved in IVA fed animals ( p 〈 0.01). IVA decreased atherosclerotic plaque size in the aortic root by 〉 40% and in the ascending aorta by 〉 70%, p 〈 0.05. HR reduction had no effect on the number of endothelial progenitor cells in the blood and the bone marrow and did not alter aortic eNOS, p-Akt, VCAM-1 or ICAM-1 expression, but decreased MCP-1 mRNA to 26 ± 7% (p 〈 0.05). IVA reduced vascular NADPH oxidase activity to 48 ± 6% and decreased L-012 chemiluminescence to 24 ± 9% (both p 〈 0.05). Lipidperoxidation was reduced to 65 ± 8% in the vasculature of the IVA group compared to vehicle treatment (p 〈 0.05). DHE fluorescence microscopy in aortic sections detected reduction of ROS release to 62 ± 4% in IVA treated mice (p 〈 0.01). The in vivo effects of IVA were absent at a dose that did not lower HR and were absent in aortic rings treated ex vivo . Protein expression of p-Akt, eNOS and p-eNOS was not altered in cultured endothelial cells (EC) by increasing doses of Iva. Similarly, NADPH oxidase activity in EC was not changed as well as the Ang II induced free radical release in vascular smooth muscle cells (DCF-fluorescence). Conclusions: Selective HR reduction improves endothelial function and reduces atherosclerotic plaque formation in ApoE −/− mice. Those effects are in part mediated by decreased markers of oxidative stress and downregulation of MCP-1. The control experiments show that a direct effect of IVA on vascular cells is unlikely and support the reduction of heart rate as the primary mechanism of action.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.118.suppl_18.S_379-e
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2008
    detail.hit.zdb_id: 1466401-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Diabetes : A Risk Factor for Catheter-Associated Infections
    BMJ ; 2015
    In:  Regional Anesthesia and Pain Medicine Vol. 40, No. 1 ( 2015), p. 16-21
    Details
    In: Regional Anesthesia and Pain Medicine, BMJ, Vol. 40, No. 1 ( 2015), p. 16-21
    Type of Medium: Online Resource
    ISSN: 1098-7339
    URL: Article
    DOI: 10.1097/AAP.0000000000000196
    Language: English
    Publisher: BMJ
    Publication Date: 2015
    detail.hit.zdb_id: 2028901-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Vascular Effects of Diet Supplementation With Plant Sterols
    Elsevier BV ; 2008
    In:  Journal of the American College of Cardiology Vol. 51, No. 16 ( 2008-04), p. 1553-1561
    Details
    In: Journal of the American College of Cardiology, Elsevier BV, Vol. 51, No. 16 ( 2008-04), p. 1553-1561
    Type of Medium: Online Resource
    ISSN: 0735-1097
    URL: Article
    DOI: 10.1016/j.jacc.2007.09.074
    RVK:
    XA 17760
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2008
    detail.hit.zdb_id: 1468327-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Heart Rate Reduction by Ivabradine Reduces Oxidative Stress, Improves Endothelial Function, and Prevents Atherosclerosis in Apolipoprotein E–Deficient Mice
    Ovid Technologies (Wolters Kluwer Health) ; 2008
    In:  Circulation Vol. 117, No. 18 ( 2008-05-06), p. 2377-2387
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 117, No. 18 ( 2008-05-06), p. 2377-2387
    Abstract: Background— Elevated heart rate is associated with increased cardiovascular morbidity. We hypothesized that selective heart rate reduction may influence endothelial function and atherogenesis and tested the effects of the I (f) current inhibitor ivabradine in apolipoprotein E–deficient mice. Methods and Results— Male apolipoprotein E–deficient mice fed a high-cholesterol diet were treated with ivabradine (10 mg · kg −1 · d −1 ) or vehicle for 6 weeks (n=10 per group). Ivabradine reduced heart rate by 13.4% (472±9 versus 545±11 bpm; P 〈 0.01) but did not alter blood pressure or lipid levels. Endothelium-dependent relaxation of aortic rings was significantly improved in ivabradine-fed animals ( P 〈 0.01). Ivabradine decreased atherosclerotic plaque size in the aortic root by 〉 40% and in the ascending aorta by 〉 70% ( P 〈 0.05). Heart rate reduction by ivabradine had no effect on the number of endothelial progenitor cells and did not alter aortic endothelial nitric oxide synthase, phosphorylated Akt, vascular cell adhesion molecule-1, or intercellular adhesion molecule-1 expression but decreased monocyte chemotactic protein-1 mRNA and exerted potent antioxidative effects. Ivabradine reduced vascular NADPH oxidase activity to 48±6% and decreased markers of superoxide production and lipid peroxidation in the aortic wall ( P 〈 0.05). The in vivo effects of ivabradine were absent at a dose that did not lower heart rate, in aortic rings treated ex vivo, and in cultured vascular cells. In contrast to ivabradine, treatment with hydralazine (25 mg · kg −1 · d −1 for 6 weeks) reduced blood pressure (−15%) but increased heart rate (37%) and did not improve endothelial function, atherosclerosis, or oxidative stress. Conclusions— Selective heart rate reduction with ivabradine decreases markers of vascular oxidative stress, improves endothelial function, and reduces atherosclerotic plaque formation in apolipoprotein E–deficient mice.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.107.746537
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2008
    detail.hit.zdb_id: 1466401-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...