Circadian variation in vascular tone and endothelial cell function in normal males

Khalid Elherik, Faisel Khan, Margaret McLaren, Gwen Kennedy, Jill J. F. Belch

    Research output: Contribution to journalArticle

    77 Citations (Scopus)

    Abstract

    The existence of circadian rhythms in the time of onset of acute cardiovascular events has been described previously. This report describes the circadian variation in endothelial cell products, such as nitric oxide (NO) and endothelin-1 (ET-1) levels, and endothelium-dependent and -independent vasodilation in normal males. Plasma ET-1 and NO were measured every 4 h in nine subjects (20-41 years old) over a 24 h period. Endothelium-dependent and -independent vascular responses were measured in the forearm skin every 4 h using laser Doppler imaging after iontophoresis of increasing doses of acetylcholine (ACh) and sodium nitroprusside respectively. A statistically significant circadian variation was demonstrated for the mean ACh response
    (P = 0.0001, ANOVA). The peak response [in arbitrary perfusion units (AU)] occurred at 16.00 hours (8.90±1.91 AU) and the lowest response at 08.00 hours (4.57±0.66 AU). A significant circadian variation was also seen for the highest dose of sodium nitroprusside (P =0.036, ANOVA), the peak occurred at 16.00 hours (3.97±1.80 AU), and the lowest at 04.00 hours (2.62±0.58 AU) and 08.00 hours (2.58±1.16 AU). There was a significant circadian variation in
    the ET-1 levels (P = 0.04) with two peaks, one at 20.00 hours (0.80±0.28 pg/ml) and the other at 08.00 hours (0.84±0.15 pg/ml). The lowest value occurred at 16.00 hours (0.61±0.24 pg/ml). There was also a borderline trend for a circadian variation in NO levels (P = 0.06), with higher levels at 20.00 hours (15.53±8.42 µmol/l), and low levels at 04.00 hours (10.87±4.70 µmol/l) and 08.00 hours (9.82±3.15 µmol/l). ACh responses were significantly correlated with ET-1 (r = -0.3, P =0.02) and NO (r = 0.30, P = 0.02) levels. Our findings suggest that endothelial activity has a circadian variation with attenuation in the morning. These circadian variations in endothelial activity might play an important role in the occurrence of acute cardiovascular events at this time, which are precipitated through the interplay between ET-1, NO and vascular function.
    Original languageEnglish
    Pages (from-to)547-552
    Number of pages6
    JournalClinical Science
    Volume102
    Issue number5
    Early online date18 Apr 2002
    Publication statusPublished - May 2002

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    Endothelin-1
    Endothelial Cells
    Perfusion
    Nitric Oxide
    Acetylcholine
    Nitroprusside
    Endothelium
    Blood Vessels
    Analysis of Variance
    Iontophoresis
    Circadian Rhythm
    Forearm
    Vasodilation
    Lasers
    Skin

    Cite this

    @article{637a8eda9c804e62b046bd9b1e9664cc,
    title = "Circadian variation in vascular tone and endothelial cell function in normal males",
    abstract = "The existence of circadian rhythms in the time of onset of acute cardiovascular events has been described previously. This report describes the circadian variation in endothelial cell products, such as nitric oxide (NO) and endothelin-1 (ET-1) levels, and endothelium-dependent and -independent vasodilation in normal males. Plasma ET-1 and NO were measured every 4 h in nine subjects (20-41 years old) over a 24 h period. Endothelium-dependent and -independent vascular responses were measured in the forearm skin every 4 h using laser Doppler imaging after iontophoresis of increasing doses of acetylcholine (ACh) and sodium nitroprusside respectively. A statistically significant circadian variation was demonstrated for the mean ACh response(P = 0.0001, ANOVA). The peak response [in arbitrary perfusion units (AU)] occurred at 16.00 hours (8.90±1.91 AU) and the lowest response at 08.00 hours (4.57±0.66 AU). A significant circadian variation was also seen for the highest dose of sodium nitroprusside (P =0.036, ANOVA), the peak occurred at 16.00 hours (3.97±1.80 AU), and the lowest at 04.00 hours (2.62±0.58 AU) and 08.00 hours (2.58±1.16 AU). There was a significant circadian variation inthe ET-1 levels (P = 0.04) with two peaks, one at 20.00 hours (0.80±0.28 pg/ml) and the other at 08.00 hours (0.84±0.15 pg/ml). The lowest value occurred at 16.00 hours (0.61±0.24 pg/ml). There was also a borderline trend for a circadian variation in NO levels (P = 0.06), with higher levels at 20.00 hours (15.53±8.42 µmol/l), and low levels at 04.00 hours (10.87±4.70 µmol/l) and 08.00 hours (9.82±3.15 µmol/l). ACh responses were significantly correlated with ET-1 (r = -0.3, P =0.02) and NO (r = 0.30, P = 0.02) levels. Our findings suggest that endothelial activity has a circadian variation with attenuation in the morning. These circadian variations in endothelial activity might play an important role in the occurrence of acute cardiovascular events at this time, which are precipitated through the interplay between ET-1, NO and vascular function.",
    author = "Khalid Elherik and Faisel Khan and Margaret McLaren and Gwen Kennedy and Belch, {Jill J. F.}",
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    Circadian variation in vascular tone and endothelial cell function in normal males. / Elherik, Khalid; Khan, Faisel; McLaren, Margaret; Kennedy, Gwen; Belch, Jill J. F.

    In: Clinical Science, Vol. 102, No. 5, 05.2002, p. 547-552.

    Research output: Contribution to journalArticle

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    T1 - Circadian variation in vascular tone and endothelial cell function in normal males

    AU - Elherik, Khalid

    AU - Khan, Faisel

    AU - McLaren, Margaret

    AU - Kennedy, Gwen

    AU - Belch, Jill J. F.

    PY - 2002/5

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    N2 - The existence of circadian rhythms in the time of onset of acute cardiovascular events has been described previously. This report describes the circadian variation in endothelial cell products, such as nitric oxide (NO) and endothelin-1 (ET-1) levels, and endothelium-dependent and -independent vasodilation in normal males. Plasma ET-1 and NO were measured every 4 h in nine subjects (20-41 years old) over a 24 h period. Endothelium-dependent and -independent vascular responses were measured in the forearm skin every 4 h using laser Doppler imaging after iontophoresis of increasing doses of acetylcholine (ACh) and sodium nitroprusside respectively. A statistically significant circadian variation was demonstrated for the mean ACh response(P = 0.0001, ANOVA). The peak response [in arbitrary perfusion units (AU)] occurred at 16.00 hours (8.90±1.91 AU) and the lowest response at 08.00 hours (4.57±0.66 AU). A significant circadian variation was also seen for the highest dose of sodium nitroprusside (P =0.036, ANOVA), the peak occurred at 16.00 hours (3.97±1.80 AU), and the lowest at 04.00 hours (2.62±0.58 AU) and 08.00 hours (2.58±1.16 AU). There was a significant circadian variation inthe ET-1 levels (P = 0.04) with two peaks, one at 20.00 hours (0.80±0.28 pg/ml) and the other at 08.00 hours (0.84±0.15 pg/ml). The lowest value occurred at 16.00 hours (0.61±0.24 pg/ml). There was also a borderline trend for a circadian variation in NO levels (P = 0.06), with higher levels at 20.00 hours (15.53±8.42 µmol/l), and low levels at 04.00 hours (10.87±4.70 µmol/l) and 08.00 hours (9.82±3.15 µmol/l). ACh responses were significantly correlated with ET-1 (r = -0.3, P =0.02) and NO (r = 0.30, P = 0.02) levels. Our findings suggest that endothelial activity has a circadian variation with attenuation in the morning. These circadian variations in endothelial activity might play an important role in the occurrence of acute cardiovascular events at this time, which are precipitated through the interplay between ET-1, NO and vascular function.

    AB - The existence of circadian rhythms in the time of onset of acute cardiovascular events has been described previously. This report describes the circadian variation in endothelial cell products, such as nitric oxide (NO) and endothelin-1 (ET-1) levels, and endothelium-dependent and -independent vasodilation in normal males. Plasma ET-1 and NO were measured every 4 h in nine subjects (20-41 years old) over a 24 h period. Endothelium-dependent and -independent vascular responses were measured in the forearm skin every 4 h using laser Doppler imaging after iontophoresis of increasing doses of acetylcholine (ACh) and sodium nitroprusside respectively. A statistically significant circadian variation was demonstrated for the mean ACh response(P = 0.0001, ANOVA). The peak response [in arbitrary perfusion units (AU)] occurred at 16.00 hours (8.90±1.91 AU) and the lowest response at 08.00 hours (4.57±0.66 AU). A significant circadian variation was also seen for the highest dose of sodium nitroprusside (P =0.036, ANOVA), the peak occurred at 16.00 hours (3.97±1.80 AU), and the lowest at 04.00 hours (2.62±0.58 AU) and 08.00 hours (2.58±1.16 AU). There was a significant circadian variation inthe ET-1 levels (P = 0.04) with two peaks, one at 20.00 hours (0.80±0.28 pg/ml) and the other at 08.00 hours (0.84±0.15 pg/ml). The lowest value occurred at 16.00 hours (0.61±0.24 pg/ml). There was also a borderline trend for a circadian variation in NO levels (P = 0.06), with higher levels at 20.00 hours (15.53±8.42 µmol/l), and low levels at 04.00 hours (10.87±4.70 µmol/l) and 08.00 hours (9.82±3.15 µmol/l). ACh responses were significantly correlated with ET-1 (r = -0.3, P =0.02) and NO (r = 0.30, P = 0.02) levels. Our findings suggest that endothelial activity has a circadian variation with attenuation in the morning. These circadian variations in endothelial activity might play an important role in the occurrence of acute cardiovascular events at this time, which are precipitated through the interplay between ET-1, NO and vascular function.

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