Regulation of Vascular Reactivity in Scleroderma: New Insights into Raynaud's Phenomenon

Flavahan, Nicholas A.

doi:10.1016/j.rdc.2007.12.005

Cited by 42 publications

(28 citation statements)

References 34 publications

(7 reference statements)

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“…The role of the RhoA/Rho kinase (ROCK) pathway in mediating vasoconstriction after local cooling in healthy subjects has been confirmed in vivo (31). Indeed, cold-induced activation of ROCK may initiate constriction, mediated by both ␣ 2C -adrenoreceptors (through their mobilization from the Golgi apparatus to the vascular smooth muscle plasma membrane) and direct calcium sensitization (10). Therefore, an impaired signal transduction pathway could be involved in the pathophysiology of RP (10), but this remains to be confirmed.…”

mentioning

confidence: 94%

Impaired transient vasodilation and increased vasoconstriction to digital local cooling in primary Raynaud's phenomenon

Roustit

Blaise

Millet

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Raynaud's phenomenon (RP) is defined as episodic ischemia of the extremities in response to cold. Although the structure of skin capillaries is normal in primary RP, some data suggest impairment of microvascular function. We aimed at testing whether digital skin blood flow was lower in RP than in controls while cooling locally. We further evaluated the contribution of sensory nerves in the response. We recruited 21 patients with primary RP and 20 healthy volunteers matched on age and gender. After a 10-min baseline at 33°C, skin temperature was cooled at 15 or 24°C during 30 min on the forearm and the finger while monitoring perfusion with a custom-design laser Doppler flowmetry probe. Perfusion was also assessed after topical anesthesia. Blood flow was expressed as cutaneous vascular conductance (CVC). Data were subsequently expressed as area above the curve (AAC0 -30) of the percentage decrease from baseline CVC (%BL). CVC on the dorsum of the finger was lower in RP patients compared with controls at 15°C (AAC0 -30 were 106,237.2 and 69,544.3%BL·s, respectively; P ϭ 0.02) and at 24°C (AAC0 -30 were 86,915 and 57,598%BL·s, respectively; P ϭ 0.04) whereas we observed no significant difference on the finger pad and the forearm. Topical anesthesia increased CVC in patients with RP (P ϭ 0.05), whereas it did not affect reactivity in controls (P ϭ 0.86). Our study shows exaggerated skin microvascular vasoconstriction to local cooling on the dorsum of the finger in primary RP compared with controls. Part of this abnormal response in primary RP depends on sensitive nerves. microcirculation; skin blood flow FIRST DESCRIBED BY MAURICE RAYNAUD in 1862 (25), Raynaud's phenomenon (RP) is defined as episodic ischemia of the extremities in response to cold or emotional stimuli, often accompanied by pain. It presents clinically as pallor, cyanosis, and often rubor of the skin. Pallor indicates vasospasm and decreased blood flow, and cyanosis is a sign of deoxygenation of the static venous blood, while rubor implies reactive hyperemia (2). RP can be primary (i.e., idiopathic) or secondary to a connective tissue disease. The pathophysiology of primary RP is multifactorial and complex, with both vascular and neural abnormalities (7,15). Although available evidence suggests that microvascular function is impaired in primary RP, the exact mechanism of such dysfunction remains poorly understood.

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confidence: 94%

Impaired transient vasodilation and increased vasoconstriction to digital local cooling in primary Raynaud's phenomenon

Roustit

Blaise

Millet

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…After a cold stimulus, SSc patients show a knowingly exacerbated response to acute ischemia, with sudden increase in vascular tonus, marked reduction of the blood flow, and even possible closure of digital arterioles. 18,19 The consistent and objective reproduction, in clinical practice, of the vasospastic events in patients with primary or secondary RyP is difficult. Several methods for the objective measurement of the severity of cold vasoreactivity in each patient with RyP, such as thermography, digital systolic blood pressure, fingertip lacticemy, plethysmography, conventional Laser Doppler, and LDI, are used.…”

Section: Discussionmentioning

confidence: 99%

Laser Doppler Imaging para quantificação do fluxo sanguíneo de polpa digital em condições basais e após estímulo frio em pacientes com esclerose sistêmica

Corrêa¹,

Perazzio²,

Andrade³

et al. 2010

Rev. Bras. Reumatol.

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“…In a recent review, Flavahan states that cold-induced vasoconstriction is a normal cutaneous response to protect the normal host from heat loss [190]. The major mediator of regulation of the cutaneous thermoregulatory vessels is via the sympathetic nerve activity through the neurotransmitter norepinephrine (NE).…”

Section: Vascular Reactivitymentioning

confidence: 99%

“…Flavahan's laboratory has discovered that the subtype α 2c -AR is thermosensitive and is upregulated on smooth muscle during cold exposure. Increased expression of α 2c -AR occurs following vascular stress including oxidative stress via the Rho-kinase pathway [190]. Abnormal reactivity of vessels in scleroderma via this pathway is suggested by the finding of increased sensitivity of vascular smooth muscle α 2 -AR expression in scleroderma skin vessels [191] (see "Treatment of scleroderma vascular disease").…”

Section: Vascular Reactivitymentioning

confidence: 99%

Vascular Disease in Scleroderma

Wigley

2008

Clinic Rev Allerg Immunol

110

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Although scleroderma is generally considered a fibrosing disease of the tissues, it is now recognized that the underlying vascular disease is playing a fundamental role in its pathogenesis and associated tissue injury. The exact mechanism for the widespread scleroderma vascular disease is still unknown, but endothelial cell injury induced by infection, immune-mediated cytotoxicity, antiendothelial antibodies, and/or ischemia-reperfusion have all been implicated. The downstream effects of blood vessel perturbation produce "biomarkers" of vascular damage that reflect disease and may predict clinical outcomes. A complex interaction between endothelial cells, smooth muscle cells, extracellular matrix, and intravascular circulating factors is now recognized to contribute to the vascular reactivity, remodeling, and occlusive disease of scleroderma. Understanding the mechanisms underlying these processes provides rationale of novel therapeutic strategies and specific targeted therapy. This review will outline some of the evidence for the causes and consequences of scleroderma vascular disease.

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Regulation of Vascular Reactivity in Scleroderma: New Insights into Raynaud's Phenomenon

Cited by 42 publications

References 34 publications

Impaired transient vasodilation and increased vasoconstriction to digital local cooling in primary Raynaud's phenomenon

Impaired transient vasodilation and increased vasoconstriction to digital local cooling in primary Raynaud's phenomenon

Laser Doppler Imaging para quantificação do fluxo sanguíneo de polpa digital em condições basais e após estímulo frio em pacientes com esclerose sistêmica

Vascular Disease in Scleroderma

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