alpha-Adrenoceptors and cold-induced vasoconstriction in human finger skin

Ekenvall, Lena; Lindblad, Lars Erik; Norbeck, Oscar; Etzell, Britt‐Marie

doi:10.1152/ajpheart.1988.255.5.h1000

Cited by 91 publications

(85 citation statements)

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“…Activation of ␣ 1 or ␣ 2 adrenoceptors caused vasoconstriction, but local cooling of the finger enhanced only the vasoconstriction to the ␣ 2 agonist. 37 Similar results were obtained by Freedman and coworkers. 38 More recently, in vitro myograph studies of murine tail arteries indicated that the cold-induced adrenergic contraction was largely due to activation of the ␣ 2c subtype of adrenoceptors.…”

Section: The Distinctive Distribution Of Adrenergic Receptorssupporting

confidence: 83%

Mechanisms of Raynaud’s disease

2005

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Raynaud's phenomenon is due to transient cessation of blood flow to the digits of the hands or feet. An attack of Raynaud’s phenomenon is classically manifested as triphasic color changes. The white phase is due to excessive vasoconstriction and cessation of regional blood flow. This phase is followed by a cyanotic phase, as the residual blood in the finger desaturates. The red phase is due to hyperemia as the attack subsides and blood flow is restored. An attack is frequently associated with pain and/or paresthesia due to sensory nerve ischemia. Variants of Raynaud’s phenomenon include acrocyanosis and primary livedo reticularis, each of which is associated with reduced skin blood flow, exacerbated by cold or emotional upset. Raynaud’s phenomenon in the absence of other disorders is primary Raynaud’s phenomenon, or Raynaud’s disease. The mechanisms of Raynaud’s disease include increased activation of the sympathetic nerves, in response to cold or emotion; an impaired habituation of the cardiovascular response to stress may contribute. In addition, there appears to be a local fault, which is likely multifactorial. This local fault is due to an alteration in vascular function rather than vascular structure. The alteration in vascular function may be related to increased sensitivity to cold of the adrenergic receptors on the digital artery vascular smooth muscle. In some cases, locally released or systemically circulating vasoconstrictors may participate, including endothelin, 5-hydroxytryptamine and thromboxane. A deficiency or increased degradation of nitric oxide, possibly due to increased oxidative stress, may be involved in some cases. These recent pathophysiological insights may lead to new therapeutic options.

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Section: The Distinctive Distribution Of Adrenergic Receptorssupporting

confidence: 83%

Mechanisms of Raynaud’s disease

2005

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“…During the first 10 min of local cooling, an immediate and pronounced VC occurs that can be inhibited by either presynaptic sympatholytics or adrenoceptor antagonists (specifically ␣ 2 ) but not with proximal nerve blockade, suggesting a localized (i.e., nonreflex) mechanism dependent on norepinephrine of sympathetic origin binding to ␣ 2 -adrenoceptors (9,12,14,19,24,27,34). The results from the present study help to further clarify the mechanisms underlying this early-phase response to cooling.…”

Section: Discussionmentioning

confidence: 52%

“…fasudil; local cooling; vascular function; adrenergic; norepinephrine CUTANEOUS VASOCONSTRICTION (VC) is the initial thermoregulatory response to defend against cold exposure, effectively minimizing heat loss to the environment. Whole body skin cooling evokes reflex VC, which involves the release of norepinephrine and sympathetic cotransmitters from sympathetic adrenergic axon terminals (38 -40, 42), whereas localized cooling of the cutaneous blood vessels and surrounding tissue engages local (i.e., nonreflex) VC mechanisms that are mediated, in part, by ␣ 2 -adrenoceptors (12,14,27,34). Reflex and local VC are not mutually exclusive responses and often operate in concert during cold exposure to maximize VC (1).…”

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confidence: 99%

Cold-induced cutaneous vasoconstriction is mediated by Rho kinase in vivo in human skin

Thompson-Torgerson

Holowatz

Flavahan

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

103

108

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Thompson-Torgerson CS, Holowatz LA, Flavahan NA, Kenney WL. Cold-induced cutaneous vasoconstriction is mediated by Rho kinase in vivo in human skin. Am J Physiol Heart Circ Physiol 292: H1700-H1705, 2007. First published December 15, 2006; doi:10.1152/ajpheart.01078.2006 is the initial thermoregulatory response to cold exposure and can be elicited through either whole body or localized skin cooling. However, the mechanisms governing local cold-induced VC are not well understood. We tested the hypothesis that Rho kinase participates in local cold-induced cutaneous VC. In seven men and women (20 -27 yr of age), up to four ventral forearm skin sites were instrumented with intradermal microdialysis fibers for localized drug delivery during cooling. Skin blood flow was monitored at each site with laserDoppler flowmetry while local skin temperature was decreased and maintained at 24°C for 40 min. Cutaneous vascular conductance (CVC; laser-Doppler flowmetry/mean arterial pressure) was expressed as percent change from 34°C baseline. During the first 5 min of cooling, CVC decreased at control sites (lactated Ringer solution) to Ϫ45 Ϯ 6% (P Ͻ 0.001), increased at adrenoceptor-antagonized sites (yohimbine ϩ propranolol) to 15 Ϯ 14% (P ϭ 0.002), and remained unchanged at both Rho kinase-inhibited (fasudil) and adrenoceptor-antagonized ϩ Rho kinase-inhibited sites (yohimbine ϩ propranolol ϩ fasudil) (Ϫ9 Ϯ 1%, P ϭ 0.4 and Ϫ6 Ϯ 2%, P ϭ 0.4, respectively). During the last 5 min of cooling, CVC further decreased at all sites when compared with baseline values (control, Ϫ77 Ϯ 4%, P Ͻ 0.001; adrenoceptor antagonized, Ϫ61 Ϯ 3%, P Ͻ 0.001; Rho kinase inhibited, Ϫ34 Ϯ 7%, P Ͻ 0.001; and adrenoceptor antagonized ϩ Rho kinase inhibited sites, Ϫ35 Ϯ 3%, P Ͻ 0.001). Rho kinase-inhibited and combined treatment sites were significantly attenuated when compared with both adrenoceptor-antagonized (P Ͻ 0.01) and control sites (P Ͻ 0.0001). Rho kinase mediates both earlyand late-phase cold-induced VC, supporting in vitro findings and providing a putative mechanism through which both adrenergic and nonadrenergic cold-induced VC occurs in an in vivo human thermoregulatory model. fasudil; local cooling; vascular function; adrenergic; norepinephrine CUTANEOUS VASOCONSTRICTION (VC) is the initial thermoregulatory response to defend against cold exposure, effectively minimizing heat loss to the environment. Whole body skin cooling evokes reflex VC, which involves the release of norepinephrine and sympathetic cotransmitters from sympathetic adrenergic axon terminals (38 -40, 42), whereas localized cooling of the cutaneous blood vessels and surrounding tissue engages local (i.e., nonreflex) VC mechanisms that are mediated, in part, by ␣ 2 -adrenoceptors (12,14,27,34). Reflex and local VC are not mutually exclusive responses and often operate in concert during cold exposure to maximize VC (1). However, whereas reflex VC mechanisms are relatively well understood, the mechanisms that govern local cold-induced VC have not been fully elucidated.Localized ...

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“…9,25 Cold stimulation rapidly increases an endogenous noradrenaline concentration, which, in turn, causes -adrenoceptor-mediated vasoconstriction and a reduction in blood flow. 26 This method is used for the evaluation of autonomic failure, 25,27,28 including Shy-Drager syndrome, Parkinson's disease, amyloidosis and diabetic neuropathy. We demonstrated that 1-adrenoceptor antagonists, which could induce orthostatic hypotension, suppress the finger skin vasoconstrictor response and the degree of the suppression is correlated with the drug plasma concentration.…”

Section: Discussionmentioning

confidence: 99%

Effect of Amezinium Metilsulfate on the Finger Skin Vasoconstrictor Response to Cold Stimulation and Venoconstrictor Response to Noradrenaline

et al. 1998

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hen a person assumes an upright posture, an increase of sympathetic outflow and an inhibition of parasympathetic activity occur reflexly, 1,2 which increases the heart rate and vascular resistance in order to maintain systemic blood pressure. Orthostatic hypotension may be caused by failure of these responses, 3,4 and for the treatment it is important to select a drug considering its pharmacological properties and the pathophysiology of the disease. At present, vasoconsticting agents are often used for the treatment of orthostatic hypotension. To understand the mechanism of these drugs, their effects not only on systemic blood pressure but also on the vasoconstrictor response to sympathetic stimulation should be examined. However, to our knowledge, such information is limited.Amezinium metilsulfate (amezinium) is one of the most popular drugs in Japan for the treatment of orthostatic hypotension. Amezinium has a unique mechanism of vasoconstriction; that is, it inhibits monoamine oxidase (MAO) activity and uptake of noradrenaline, 5,6 which prompted us to examine whether it influences the vasoconstrictor response to sympathetic stimulation and to -adrenoceptor stimulation by noradrenaline in humans.To examine the effects of the drug, the following 2 methods were thought to be suitable and were used in the present study, because they are sensitive and noninvasive and are used for the evaluation of autonomic disturbances or orthostatic hypotension. First, the finger-tip vasoconstrictor response to cold stimulation on the contralateral hand was examined using a laser Doppler flowmeter, which is an appropriate means for the study of the vasomotor response mediated by -adrenoceptor stimulation. 7,8 Second, the venoconstrictor response to locally infused noradrenaline was examined using a linear variable differential transformer (LVDT), which provides a sensitive and easy reproducible means of assessing the effect of a drug on peripheral veins. 9 As the decrease in venous blood return to the heart is involved in the pathogenesis of orthostatic hypotension, 3 it is interesting to also examine the effect of these drugs on veins.In the present study, we examined, using these methods, the effects of amezinium on the vasoconstrictor responses, and compared them in healthy subjects with those of midodrine hydrochloride (midodrine), an 1-adrenoceptor agonist, 10 which is also a popular drug for orthostatic hypotention. Methods SubjectsEight healthy Japanese males (21-26 years, 64-78 kg) were selected. They were normotensive and nonsmokers, without concomitant medication for at least 2 weeks before the study. The study was approved by the Ethical Committee of Jichi Medical School and all subjects gave their informed consent.Jpn Circ J 1998; 62: 824 -828 (Received April 10, 1998; revised manuscript received July 9, 1998; accepted July 14, 1998 Orthostatic hypotension can be caused by an inadequate vasoconstrictor response. The effects of amezinium on vasoconstrictor response to sympathetic stimulation and to exogenous noradre...

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alpha-Adrenoceptors and cold-induced vasoconstriction in human finger skin

Cited by 91 publications

References 0 publications

Mechanisms of Raynaud’s disease

Mechanisms of Raynaud’s disease

Cold-induced cutaneous vasoconstriction is mediated by Rho kinase in vivo in human skin

Effect of Amezinium Metilsulfate on the Finger Skin Vasoconstrictor Response to Cold Stimulation and Venoconstrictor Response to Noradrenaline

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