The human cutaneous circulation as a model of generalized microvascular function

Holowatz, Lacy A.; Thompson-Torgerson, Caitlin S.; Kenney, W. Larry

doi:10.1152/japplphysiol.00858.2007

Cited by 395 publications

(355 citation statements)

References 34 publications

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“…The present results support, at least in normothermia, the suggestion that the cutaneous circulation constitutes a potentially representative vascular bed to examine the mechanisms of microcirculatory function and dysfunction (13). Because the forearm has been exclusively used as a model for studying vascular function, it has become common to extrapolate the findings obtained from this vascular bed to the rest of the body.…”

Section: Discussionsupporting

confidence: 85%

Limb-specific differences in the skin vascular responsiveness to adrenergic agonists

Yamazaki

Yuge

2011

Journal of Applied Physiology

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Yamazaki F, Yuge N. Limb-specific differences in the skin vascular responsiveness to adrenergic agonists. J Appl Physiol 111: 170-176, 2011. First published April 28, 2011 doi:10.1152/japplphysiol.00068.2011In this study, to test the hypothesis that adrenergic vasoconstrictor responses of the legs are greater compared with the arms in human skin, cutaneous vascular conductance (CVC) in the forearm and calf were compared during the infusion of adrenergic agonists in healthy young volunteers. Under normothermic conditions, norepinephrine (NE, ␣-and ␤-agonist, 1 ϫ 10 Ϫ8 to 1 ϫ 10 Ϫ2 M), phenylephrine (PHE, ␣1-agonist, 1 ϫ 10 Ϫ8 to 1 ϫ 10 Ϫ2 M), dexmedetomidine (DEX, ␣2-agonist, 1 ϫ 10 Ϫ9 to 1 ϫ 10 Ϫ4 M), and isoproterenol (ISO, ␤-agonist, 1 ϫ 10 Ϫ8 to 1 ϫ 10 Ϫ3 M) were administered by intradermal microdialysis. Skin blood flow (SkBF) was measured by laserDoppler flowmetry, and the local temperature at SkBF-measuring sites was maintained at 34°C throughout the experiments. CVC was calculated as the ratio of SkBF to blood pressure and expressed relative to the baseline value before drug infusion. The dose of NE at the onset of vasoconstriction and the effective dose (ED50) resulting in 50% of the maximal vasoconstrictor response for NE were lower (P Ͻ 0.001) in the calf than forearm. The ED50 for PHE and DEX was also lower (P Ͻ 0.05) in the calf than forearm. Increases in CVC in response to ISO were potentially smaller in the calf, but the statistical differences in the responses were dependent on the expressions of CVC. These findings suggest that the cutaneous vasoconstrictor responsiveness to exogenous NE is greater in the legs than in the arms due to a higher ␣1-and ␣2-adrenoceptor reactivity, while the ␤-adrenoceptor function plays a minor role in regional differences in adrenergic vasoconstriction in normothermic humans. skin blood flow; exogenous norepinephrine; ␣-adrenergic receptor; ␤-adrenergic receptor; microdialysis IN HUMANS, peripheral vasoconstrictor responses to upright posture show heterogeneity between the upper and lower limbs (14,16,22,48). The findings from previous studies suggest that the leg vasculature is more responsive to orthostatic stimulation than the arm vasculature. The augmented vasoconstrictor response observed in the human lower-leg vasculature is influenced by sympathetic and local mechanisms (14,22,24,38) and could play an important regulatory role by limiting the degree to which blood accumulates in the legs during orthostatic stress (29,30).The vasoconstrictor response to the upright posture is via reflex and nonreflex (e.g., venoarteriolar response) mechanisms. The reflex vasoconstriction is influenced by centrally driven activity in sympathetic vasoconstrictor nerves and postjunctional adrenergic receptor responsiveness. With regard to the central sympathetic outflow, similar increases in muscle sympathetic nerve activity have been shown in the arm and leg during orthostatic stress (14, 31). In addition, similar increases in regional norepinephrine (NE) spillover have been re...

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Section: Discussionsupporting

confidence: 85%

Limb-specific differences in the skin vascular responsiveness to adrenergic agonists

Yamazaki

Yuge

2011

Journal of Applied Physiology

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“…Recent studies have indicated that changes in the cutaneous microvasculature often mirror changes in vessels of different size (Debbabi et al, 2010) and in other vascular beds, such as the coronary microcirculation (Khan et al, 2008). In fact, increasing evidence indicates that the cutaneous microcirculation can serve as a representative model to examine mechanisms of vascular function and dysfunction that occur on a systemic level (Holowatz et al, 2008;IJzerman et al, 2003).…”

Section: In Vitro Vascular Modelsmentioning

confidence: 99%

Transdermal iontophoresis as an in-vivo technique for studying microvascular physiology

Tesselaar

Sjöberg

2011

Microvascular Research

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“…19 The aim of this study was to simultaneously examine small-(functional and anatomical skin CD) and large (pulse-wave velocity, PWV)-artery function in subjects with and without the MetS. We also investigated the associations between each component of the MetS and these vascular markers, and the risk associated with impairment in either PWV or CD.…”

Section: Introductionmentioning

confidence: 99%

Macrovascular and microvascular dysfunction in the metabolic syndrome

et al. 2010

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The metabolic syndrome (MetS) is associated with increased risk of type-2 diabetes and cardiovascular disease (CVD). We hypothesized that both small and large arteries may be impaired in subjects with the MetS, even in the absence of known CVD or diabetes. We compared both skin capillary density (CD) and pulse-wave velocity (PWV) in 36 cases with the MetS with those from 108 age-and gender-matched controls from the SU.VIM.AX-2 cohort. Compared with controls, MetS subjects demonstrated increased PWV (12.2 ± 2.8 vs. 10.7 ± 1.9 m s À1 , P¼0.005) and lower functional CD (83.1 ± 15.7 vs. 89.4 ± 14.2 capillaries per mm 2 , P¼0.03). Functional CD was inversely related to fasting glucose, triglycerides (TGs) and HOMA-IR (all Po0.05). On the other hand, no association was found between CD and BP or with PWV. In multivariate models, the odds ratios (95% confidence interval) for one standard deviation change, for having an impaired PWV (X12 m s À1 , n¼44), were: 1.65 (1.11-2.45) for systolic BP and 1.93 (1.25-2.99) for TG only. For impaired CD (p80 capillaries per mm 2 ), the odds ratios (95% confidence interval) were 1.45 (1.00-2.08) for TG and 1.65 (1.13-2.43) for fasting glucose, only. In conclusion, MetS subjects exhibited evidence of macro-and microcirculatory dysfunction, even in the absence of diabetes and CVD. The common mechanism linking MetS components to CVD risk through small-and large-artery dysfunctions may be mediated through metabolic factors related to insulin resistance, not to increased BP.

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The human cutaneous circulation as a model of generalized microvascular function

Cited by 395 publications

References 34 publications

Limb-specific differences in the skin vascular responsiveness to adrenergic agonists

Limb-specific differences in the skin vascular responsiveness to adrenergic agonists

Transdermal iontophoresis as an in-vivo technique for studying microvascular physiology

Macrovascular and microvascular dysfunction in the metabolic syndrome

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