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

Cutaneous vasoconstriction (VC) 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 laser-Doppler 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 −45 ± 6% ( P < 0.001), increased at adrenoceptor-antagonized sites (yohimbine + propranolol) to 15 ± 14% ( P = 0.002), and remained unchanged at both Rho kinase-inhibited (fasudil) and adrenoceptor-antagonized + Rho kinase-inhibited sites (yohimbine + propranolol + fasudil) (−9 ± 1%, P = 0.4 and −6 ± 2%, P = 0.4, respectively). During the last 5 min of cooling, CVC further decreased at all sites when compared with baseline values (control, −77 ± 4%, P < 0.001; adrenoceptor antagonized, −61 ± 3%, P < 0.001; Rho kinase inhibited, −34 ± 7%, P < 0.001; and adrenoceptor antagonized + Rho kinase inhibited sites, −35 ± 3%, P < 0.001). Rho kinase-inhibited and combined treatment sites were significantly attenuated when compared with both adrenoceptor-antagonized ( P < 0.01) and control sites ( P < 0.0001). Rho kinase mediates both early- and 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.

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Intradermal administration of ATP does not mitigate tyramine-stimulated vasoconstriction in human skin

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00846.2009 ◽

2010 ◽

Vol 298 (5) ◽

pp. R1417-R1420 ◽

Cited By ~ 16

Author(s):

Jonathan E. Wingo ◽

R. Matthew Brothers ◽

Juan Del Coso ◽

Craig G. Crandall

Keyword(s):

Skeletal Muscle ◽

Human Skin ◽

Cholinergic Neurons ◽

Laser Doppler ◽

Whole Body ◽

Local Skin ◽

Doppler Flowmetry ◽

Intradermal Administration ◽

Forearm Skin ◽

Cutaneous Vasoconstriction

Cutaneous vasodilation associated with whole-body heat stress occurs via withdrawal of adrenergic vasoconstriction and engagement of cholinergic “active” vasodilation, the latter of which attenuates cutaneous vasoconstrictor responsiveness. However, the precise neurotransmitter(s) responsible for this sympatholytic-like effect remain unknown. In skeletal muscle, ATP inhibits adrenergically mediated vasoconstriction. ATP also may be responsible for attenuating cutaneous vasoconstriction since it is coreleased from cholinergic neurons. The effect of ATP on cutaneous vasoconstrictor responsiveness, however, has not been investigated. Accordingly, this study tested the hypothesis that ATP inhibits adrenergically mediated cutaneous vasoconstriction. To accomplish this objective, four microdialysis probes were inserted in dorsal forearm skin of 11 healthy individuals (mean ± SD; 35 ± 11 years). Local temperature at each site was clamped at 34°C throughout the protocol. Skin blood flow was indexed by laser-Doppler flowmetry and was used to calculate cutaneous vascular conductance (CVC; laser-Doppler-derived flux/mean arterial pressure), which was normalized to peak CVC achieved with sodium nitroprusside infusion combined with local skin heating to ∼42°C. Two membranes were perfused with 30 mM ATP, while the other two membranes were flow matched via administration of 2.8 mM adenosine to serve as control sites. After achieving stable baselines, 1×10−4 M tyramine was administered at all sites, while ATP and adenosine continued to be infused at their respective sites. ATP and adenosine infusion increased CVC from baseline by 35 ± 26% CVCpeak units and by 36 ± 15% CVCpeak units, respectively ( P = 0.75). Tyramine decreased CVC similarly (by about one-third) at all sites ( P < 0.001 for main effect and P = 0.32 for interaction). These findings indicate that unlike in skeletal muscle, ATP does not attenuate tyramine-stimulated vasoconstriction in human skin.

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Nitric oxide and receptors for VIP and PACAP in cutaneous active vasodilation during heat stress in humans

Journal of Applied Physiology ◽

10.1152/japplphysiol.00859.2012 ◽

2012 ◽

Vol 113 (10) ◽

pp. 1512-1518 ◽

Cited By ~ 18

Author(s):

Dean L. Kellogg ◽

Joan L. Zhao ◽

Yubo Wu ◽

John M. Johnson

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Heat Stress ◽

Laser Doppler Flowmetry ◽

Combined Treatment ◽

Receptor Activation ◽

Laser Doppler ◽

Whole Body ◽

Pac1 Receptor ◽

Doppler Flowmetry

VPAC2 receptors sensitive to vasoactive intestinal polypeptide (VIP) and pituitary adenylyl cyclase activating polypeptide (PACAP), PAC1 receptors sensitive to PACAP, and nitric oxide (NO) generation by NO synthase (NOS) are all implicated in cutaneous active vasodilation (AVD) through incompletely defined mechanisms. We hypothesized that VPAC2/PAC1 receptor activation and NO are synergistic and interdependent in AVD and tested our hypothesis by examining the effects of VPAC2/PAC1 receptor blockade with and without NOS inhibition during heat stress. The VPAC2/PAC1 antagonist, pituitary adenylate cyclase activating peptide 6–38 (PACAP6–38) and the NOS inhibitor, NG-nitro-l-arginine methyl ester (l-NAME) were administered by intradermal microdialysis. PACAP6–38, l-NAME, a combination of PACAP6–38 and l-NAME, or Ringer's solution alone were perfused at four separate sites. Skin blood flow was monitored by laser-Doppler flowmetry at each site. Body temperature was controlled with water-perfused suits. Blood pressure was monitored by Finapres, and cutaneous vascular conductance (CVC) calculated (CVC = laser-Doppler flowmetry/mean arterial pressure). The protocol began with a 5- to 10-min baseline period without antagonist perfusion, followed by perfusion of PACAP6–38, l-NAME, or combined PACAP6–38 and l-NAME at the different sites in normothermia (45 min), followed by 3 min of whole body cooling. Whole body heating was then performed to induce heat stress and activate AVD. Finally, 58 mM sodium nitroprusside were perfused at all sites to effect maximal vasodilation for normalization of blood flow data. No significant differences in CVC (normalized to maximum) were found among Ringer's PACAP6–38, l-NAME, or combined antagonist sites during normothermia ( P > 0.05 among sites) or cold stress ( P > 0.05 among sites). CVC responses at all treated sites were attenuated during AVD ( P < 0.05 vs. Ringer's). Attenuation was greater at l-NAME and combined PACAP6–38- and l-NAME-treated sites than at PACAP6–38 sites ( P > 0.05). Because responses did not differ between l-NAME and combined treatment sites ( P > 0.05), we conclude that VPAC2/PAC1 receptors require NO in series to effect AVD.

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Fractal Dimension Characterization of in-vivo Laser Doppler Flowmetry signals

Physics Procedia ◽

10.1016/j.phpro.2011.06.124 ◽

2011 ◽

Vol 19 ◽

pp. 49-54 ◽

Cited By ~ 2

Author(s):

Gayathri Srinivasan ◽

N. Sujatha

Keyword(s):

Fractal Dimension ◽

Laser Doppler Flowmetry ◽

Laser Doppler ◽

Doppler Flowmetry

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Laser Speckle Contrast Imaging and Laser Doppler Flowmetry Exhibit Test‐Retest Reproducibility During the Reflex Cutaneous Vasoconstriction Response

The FASEB Journal ◽

10.1096/fasebj.2021.35.s1.04432 ◽

2021 ◽

Vol 35 (S1) ◽

Author(s):

Kelsey Schwartz ◽

Behnia Shirazi ◽

James Lang

Keyword(s):

Laser Doppler Flowmetry ◽

Laser Speckle ◽

Laser Doppler ◽

Contrast Imaging ◽

Doppler Flowmetry ◽

Laser Speckle Contrast Imaging ◽

Speckle Contrast ◽

Cutaneous Vasoconstriction

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A Minimally Invasive Technique for Serial Intraosseous Perfusion Measurements in the Murine Tibia Using Laser Doppler Flowmetry

10.1101/708453 ◽

2019 ◽

Cited By ~ 1

Author(s):

Nicholas J Hanne ◽

Elizabeth D Easter ◽

Sandra Stangeland-Molo ◽

Jacqueline H Cole

Keyword(s):

Minimally Invasive ◽

Laser Doppler Flowmetry ◽

Laser Doppler ◽

Invasive Technique ◽

List Type ◽

Current Standard ◽

Preclinical Research ◽

Modified Technique ◽

Doppler Flowmetry

AbstractIn biomedical and preclinical research, the current standard method for measuring blood perfusion inside murine bone, radiolabeled microspheres, is a terminal procedure that cannot be used to monitor longitudinal perfusion changes. Laser Doppler flowmetry (LDF) can quantify perfusion within the proximal tibial metaphysis of mice in vivo but requires a surgical procedure to place the measurement probe directly onto the bone surface. Sustained inflammation for over a month following this technique was previously reported, and previous studies have used LDF as an endpoint-only procedure. We developed a modified, minimally invasive LDF procedure to measure intraosseous perfusion in the murine tibia without stimulating local or systemic inflammation or inducing gait abnormalities. This modified technique can be used to measure perfusion weekly for up to at least a month. Unlike previous endpoint-only techniques, this modified LDF procedure can be performed weekly to monitor serial changes to intraosseous perfusion in the murine tibiaThe modified LDF technique utilizes a smaller, more localized incision to minimize invasiveness and speed recovery

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