Longitudinal assessment of endothelial function in the microvasculature of mice in-vivo

Jill J.F. Belch, Naveed Akbar, Venkateswara Alapati, John Petrie, Simon Arthur, Faisel Khan

    Research output: Contribution to journalArticle

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    Abstract

    Endothelial dysfunction is associated with early development of cardiovascular disease, making longitudinal measurements desirable. We devised a protocol using laser Doppler imaging (LDI) and iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to assess the skin microcirculation longitudinally in mice every 4 weeks for 24 weeks in two groups of C57BL/6 mice, chow versus high-cholesterol diet(known to induce endothelial dysfunction). LDI measurements were compared with vascular function (isometric tension) measured using wire myography in the tail artery in response to ACh and SNP. Microvascular responses to ACh were significantly reduced in cholesterol-fed versus chow-fed mice from week 4 onwards (P <0.005, ANOVA). Pre-treatment with N(G)-nitro-l-arginine methyl-ester-hydrochloride (L-NAME) showed a significant reduction in ACh response compared with vehicle-treated animals (P <0.05) at baseline and at 12 weeks. In cholesterol-fed mice, ACh responses were 226 ± 21 and 180 ± 21 AU (P = 0.03) before and after L-NAME, respectively. A reduction in ex-vivo ACh response was detected in the tail artery in cholesterol-fed mice, and a significant correlation found between peak microvascular ACh response and maximum ACh response in the tail artery (r = 0.699, P = 0.017). No changes were found in SNP responses in the microvasculature or tail artery. Using this protocol, we have shown longitudinal decreases in microvascular endothelial function to cholesterol feeding. L-NAME studies confirm that the reduced vasodilatation to ACh in cholesterol-fed mice was mediated partly through reduced NO bioavailability. Wire myography of tail arteries confirmed that in-vivo measurements of microvascular function reflect ex-vivo vascular function in other beds. Longitudinal assessments of skin microvascular function in mice could provide a useful translatable model for assessing early endothelial dysfunction.
    Original languageEnglish
    Pages (from-to)86-92
    Number of pages7
    JournalMicrovascular Research
    Volume85
    DOIs
    Publication statusPublished - Jan 2013

    Fingerprint

    Microvessels
    Acetylcholine
    Cholesterol
    Tail
    Arteries
    NG-Nitroarginine Methyl Ester
    Nitroprusside
    Myography
    Blood Vessels
    Skin
    Lasers
    Wire
    Microcirculation
    Imaging techniques
    Iontophoresis
    Nutrition
    Analysis of variance (ANOVA)
    Inbred C57BL Mouse
    Vasodilation
    Biological Availability

    Cite this

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    title = "Longitudinal assessment of endothelial function in the microvasculature of mice in-vivo",
    abstract = "Endothelial dysfunction is associated with early development of cardiovascular disease, making longitudinal measurements desirable. We devised a protocol using laser Doppler imaging (LDI) and iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to assess the skin microcirculation longitudinally in mice every 4 weeks for 24 weeks in two groups of C57BL/6 mice, chow versus high-cholesterol diet(known to induce endothelial dysfunction). LDI measurements were compared with vascular function (isometric tension) measured using wire myography in the tail artery in response to ACh and SNP. Microvascular responses to ACh were significantly reduced in cholesterol-fed versus chow-fed mice from week 4 onwards (P <0.005, ANOVA). Pre-treatment with N(G)-nitro-l-arginine methyl-ester-hydrochloride (L-NAME) showed a significant reduction in ACh response compared with vehicle-treated animals (P <0.05) at baseline and at 12 weeks. In cholesterol-fed mice, ACh responses were 226 ± 21 and 180 ± 21 AU (P = 0.03) before and after L-NAME, respectively. A reduction in ex-vivo ACh response was detected in the tail artery in cholesterol-fed mice, and a significant correlation found between peak microvascular ACh response and maximum ACh response in the tail artery (r = 0.699, P = 0.017). No changes were found in SNP responses in the microvasculature or tail artery. Using this protocol, we have shown longitudinal decreases in microvascular endothelial function to cholesterol feeding. L-NAME studies confirm that the reduced vasodilatation to ACh in cholesterol-fed mice was mediated partly through reduced NO bioavailability. Wire myography of tail arteries confirmed that in-vivo measurements of microvascular function reflect ex-vivo vascular function in other beds. Longitudinal assessments of skin microvascular function in mice could provide a useful translatable model for assessing early endothelial dysfunction.",
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    Longitudinal assessment of endothelial function in the microvasculature of mice in-vivo. / Belch, Jill J.F.; Akbar, Naveed; Alapati, Venkateswara; Petrie, John; Arthur, Simon; Khan, Faisel.

    In: Microvascular Research, Vol. 85, 01.2013, p. 86-92.

    Research output: Contribution to journalArticle

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