Oral vitamin C enhances the adrenergic vasoconstrictor response to local cooling in human skin

2012 ◽  
Vol 112 (10) ◽  
pp. 1689-1697 ◽  
Author(s):  
Fumio Yamazaki
Keyword(s):  
Human Skin ◽  
Local Administration ◽  
Adrenergic System ◽  
Local Cooling ◽  
Oral Vitamin ◽  
Vascular Conductance ◽  
Doppler Flowmetry ◽  
Vasoconstrictor Response ◽  
Forearm Skin ◽  
Cutaneous Vascular Conductance

Local administration of ascorbic acid (Asc) at a supraphysiological concentration inhibits the cutaneous vasoconstrictor response to local cooling (LC). However, whether orally ingesting Asc inhibits the LC-induced vasoconstrictor response remains unknown. The purpose of the present study was to examine the acute influence of oral Asc on the adrenergic vasoconstrictor response to LC in human skin. In experiment 1, skin blood flow (SkBF) was measured by laser-Doppler flowmetry at three sites (forearm, calf, palm). The three skin sites were locally cooled from 34 to 24°C at −1°C/min and maintained at 24°C for 20 min before (Pre) and 1.5 h after (Post) oral Asc (2-g single dose) or placebo supplementation. Cutaneous vascular conductance (CVC) was calculated as the ratio of SkBF to blood pressure and expressed relative to the baseline value before LC. Oral Asc enhanced ( P < 0.05) the reductions in CVC in the forearm (Pre, −50.3 ± 3.3%; Post, −57.8 ± 2.2%), calf (Pre, −52.6 ± 3.7%; Post, −66.1 ± 4.3%), and palm (Pre, −46.2 ± 6.2%; Post, −60.4 ± 5.6%) during LC. The placebo did not change the responses at any site. In experiment 2, to examine whether the increased vasoconstrictor response caused by oral Asc is due to the adrenergic system, the release of neurotransmitters from adrenergic nerves in forearm skin was blocked locally by iontophoresis of bretylium tosylate (BT). Oral Asc enhanced ( P < 0.05) the reductions in CVC at untreated control sites but did not change the responses at BT-treated sites during LC. In experiment 3, to further examine whether adrenergically mediated vasoconstriction is enhanced by oral Asc, 0.1 mM tyramine was administered using intradermal microdialysis in the forearm skin at 34°C in the Pre and Post periods. Oral Asc increased ( P < 0.05) the tyramine-induced reduction in CVC. These findings suggest that oral Asc acutely enhances the cutaneous vasoconstrictor responses to LC through the modification of adrenergic sympathetic mechanisms.

Sympathetic, sensory, and nonneuronal contributions to the cutaneous vasoconstrictor response to local cooling

2005 ◽  
Vol 288 (4) ◽  
pp. H1573-H1579 ◽  
Author(s):  
John M. Johnson ◽  
Tony C. Yen ◽  
Kun Zhao ◽  
Wojciech A. Kosiba
Keyword(s):  
Sensory Nerve ◽  
Sympathetic Nerves ◽  
Local Cooling ◽  
Vascular Responses ◽  
Y1 Receptor ◽  
Vasoconstrictor Response ◽  
Forearm Skin ◽  
Cold Sensitive ◽  
Cutaneous Vascular Conductance ◽  
Cutaneous Vasoconstriction

Previous work indicates that sympathetic nerves participate in the vascular responses to direct cooling of the skin in humans. We evaluated this hypothesis further in a four-part series by measuring changes in cutaneous vascular conductance (CVC) from forearm skin locally cooled from 34 to 29°C for 30 min. In part 1, bretylium tosylate reversed the initial vasoconstriction (−14 ± 6.6% control CVC, first 5 min) to one of vasodilation (+19.7 ± 7.7%) but did not affect the response at 30 min (−30.6 ± 9% control, −38.9 ± 6.9% bretylium; both P < 0.05, P > 0.05 between treatments). In part 2, yohimbine and propranolol (YP) also reversed the initial vasoconstriction (−14.3 ± 4.2% control) to vasodilation (+26.3 ± 12.1% YP), without a significant effect on the 30-min response (−26.7 ± 6.1% YP, −43.2 ± 6.5% control; both P < 0.05, P > 0.05 between sites). In part 3, the NPY Y1 receptor antagonist BIBP 3226 had no significant effect on either phase of vasoconstriction ( P > 0.05 between sites both times). In part 4, sensory nerve blockade by anesthetic cream (Emla) also reversed the initial vasoconstriction (−20.1 ± 6.4% control) to one of vasodilation (+213.4 ± 87.0% Emla), whereas the final levels did not differ significantly (−37.7 ± 10.1% control, −37.2 ± 8.7% Emla; both P < 0.05, P > 0.05 between treatments). These results indicate that local cooling causes cold-sensitive afferents to activate sympathetic nerves to release norepinephrine, leading to a local cutaneous vasoconstriction that masks a nonneurogenic vasodilation. Later, a vasoconstriction develops with or without functional sensory or sympathetic nerves.

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

2011 ◽  
Vol 111 (1) ◽  
pp. 170-176 ◽  
Author(s):  
Fumio Yamazaki ◽  
Nagisa Yuge
Keyword(s):  
Regional Differences ◽  
Minor Role ◽  
Adrenergic Agonists ◽  
Drug Infusion ◽  
Vascular Conductance ◽  
Doppler Flowmetry ◽  
Vasoconstrictor Response ◽  
Vascular Responsiveness ◽  
A Minor ◽  
Cutaneous Vascular Conductance

In 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, α- and β-agonist, 1 × 10−8 to 1 × 10−2 M), phenylephrine (PHE, α1-agonist, 1 × 10−8 to 1 × 10−2 M), dexmedetomidine (DEX, α2-agonist, 1 × 10−9 to 1 × 10−4 M), and isoproterenol (ISO, β-agonist, 1 × 10−8 to 1 × 10−3 M) were administered by intradermal microdialysis. Skin blood flow (SkBF) was measured by laser-Doppler 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 < 0.001) in the calf than forearm. The ED50 for PHE and DEX was also lower ( P < 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 α1- and α2-adrenoceptor reactivity, while the β-adrenoceptor function plays a minor role in regional differences in adrenergic vasoconstriction in normothermic humans.

Influence of hyperoxia on skin vasomotor control in normothermic and heat-stressed humans

2007 ◽  
Vol 103 (6) ◽  
pp. 2026-2033 ◽  
Author(s):  
Fumio Yamazaki ◽  
Kazuo Takahara ◽  
Ryoko Sone ◽  
John M. Johnson
Keyword(s):  
Thermal Conditions ◽  
Inhibitory Effects ◽  
Doppler Flowmetry ◽  
Vasoconstrictor Response ◽  
Forearm Skin ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Cutaneous Vascular Conductance ◽  
Male Subjects ◽  
Cutaneous Vasoconstriction

Hyperoxia induces skin vasoconstriction in humans, but the mechanism is still unclear. In the present study we examined whether the vasoconstrictor response to hyperoxia is through activated adrenergic function ( protocol 1) or through inhibitory effects on nitric oxide synthase (NOS) and/or cyclooxygenase (COX) ( protocol 2). We also tested whether any such vasoconstrictor effect is altered by body heating. In protocol 1 ( n = 11 male subjects), release of norepinephrine from adrenergic terminals in the forearm skin was blocked locally by iontophoresis of bretylium (BT). In protocol 2, the NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME) and the nonselective COX antagonist ketorolac (Keto) were separately administered by intradermal microdialysis in 11 male subjects. In the two protocols, subjects breathed 21% (room air) or 100% O2 in both normothermia and hyperthermia. Skin blood flow (SkBF) was monitored by laser-Doppler flowmetry. Cutaneous vascular conductance (CVC) was calculated as the ratio of SkBF to blood pressure measured by Finapres. In protocol 1, breathing 100% O2 decreased ( P < 0.05) CVC at the BT-treated and at untreated sites from the levels of CVC during 21% O2 breathing both in normothermia and hyperthermia. In protocol 2, the administration of l-NAME inhibited ( P < 0.05) the reduction of CVC during 100% O2 breathing in both thermal conditions. The administration of Keto inhibited ( P < 0.05) the reduction of CVC during 100% O2 breathing in hyperthermia but not in normothermia. These results suggest that skin vasoconstriction with hyperoxia is partly due to the decreased activity of functional NOS in normothermia and hyperthermia. We found no significant role for adrenergic mechanisms in hyperoxic vasoconstriction. Decreased production of vasodilator prostaglandins may play a role in hyperoxia-induced cutaneous vasoconstriction in heat-stressed humans.

Role of sensory nerves in the cutaneous vasoconstrictor response to local cooling in humans

2007 ◽  
Vol 293 (1) ◽  
pp. H784-H789 ◽  
Author(s):  
Gary J. Hodges ◽  
J. Andrew Traeger ◽  
Tri Tang ◽  
Wojciech A. Kosiba ◽  
Kun Zhao ◽  
...  
Keyword(s):  
Sensory Nerve ◽  
Sensory Nerves ◽  
Nerve Function ◽  
Local Cooling ◽  
Local Skin ◽  
Doppler Flowmetry ◽  
Vasoconstrictor Response ◽  
Cutaneous Vascular Conductance ◽  
Term Response

Local cooling (LC) causes a cutaneous vasoconstriction (VC). In this study, we tested whether there is a mechanism that links LC to VC nerve function via sensory nerves. Six subjects participated. Local skin and body temperatures were controlled with Peltier probe holders and water-perfused suits, respectively. Skin blood flow at four forearm sites was monitored by laser-Doppler flowmetry with the following treatments: untreated control, pretreatment with local anesthesia (LA) blocking sensory nerve function, pretreatment with bretylium tosylate (BT) blocking VC nerve function, and pretreatment with both LA and BT. Local skin temperature was slowly reduced from 34 to 29°C at all four sites. Both sites treated with LA produced an increase in cutaneous vascular conductance (CVC) early in the LC process (64 ± 55%, LA only; 42 ± 14% LA plus BT; P < 0.05), which was absent at the control and BT-only sites (5 ± 8 and 6 ± 8%, respectively; P > 0.05). As cooling continued, there were significant reductions in CVC at all sites ( P < 0.05). At control and LA-only sites, CVC decreased by 39 ± 4 and 46 ± 8% of the original baseline values, which were significantly ( P < 0.05) more than the reductions in CVC at the sites treated with BT and BT plus LA (−26 ± 8 and −22 ± 6%). Because LA affected only the short-term response to LC, either alone or in the presence of BT, we conclude that sensory nerves are involved early in the VC response to LC, but not for either adrenergic or nonadrenergic VC with longer term LC.

Acetylcholine-induced vasodilation is mediated by nitric oxide and prostaglandins in human skin

2005 ◽  
Vol 98 (2) ◽  
pp. 629-632 ◽  
Author(s):  
D. L. Kellogg ◽  
J. L. Zhao ◽  
U. Coey ◽  
J. V. Green
Keyword(s):  
Nitric Oxide ◽  
Human Skin ◽  
Control Site ◽  
Relative Increase ◽  
No Synthase ◽  
Vascular Conductance ◽  
Doppler Flowmetry ◽  
Endothelial Nitric Oxide ◽  
Cutaneous Vascular Conductance ◽  
Cutaneous Blood

Acetylcholine (ACh) can effect vasodilation by several mechanisms, including activation of endothelial nitric oxide (NO) synthase and prostaglandin (PG) production. In human skin, exogenous ACh increases both skin blood flow (SkBF) and bioavailable NO levels, but the relative increase is much greater in SkBF than NO. This led us to speculate ACh may dilate cutaneous blood vessels through PGs, as well as NO. To test this hypothesis, we performed a study in 11 healthy people. We measured SkBF by laser-Doppler flowmetry (LDF) at four skin sites instrumented for intradermal microdialysis. One site was treated with ketorolac (Keto), a nonselective cyclooxygenase antagonist. A second site was treated with NG-nitro-l-arginine methyl ester (l-NAME) to inhibit NO synthase. A third site was treated with a combination of Keto and l-NAME. The fourth site was an untreated control site. After the three treated sites received the different inhibiting agents, ACh was administered to all four sites by intradermal microdialysis. Finally, sodium nitroprusside (SNP) was administered to all four sites. Mean arterial pressure (MAP) was monitored by Finapres, and cutaneous vascular conductance (CVC) was calculated (CVC = LDF/MAP). For data analysis, CVC values for each site were normalized to their respective maxima as effected by SNP. The results showed that both Keto and l-NAME each attenuated the vasodilation induced by exogenous ACh (ACh control = 79 ± 4% maximal CVC, Keto = 55 ± 7% maximal CVC, l-NAME = 46 ± 6% maximal CVC; P < 0.05, ACh vs. Keto or l-NAME). The combination of the two agents produced an even greater attenuation of ACh-induced vasodilation (31 ± 5% maximal CVC; P < 0.05 vs. all other sites). We conclude that a portion of the vasodilation effected by exogenous ACh in skin is due to NO; however, a significant portion is also mediated by PGs.

The acute impact of local cooling versus local heating on human skin microcirculation using laser Doppler flowmetry and tissue spectrophotometry

Burns ◽  
2020 ◽  
Vol 46 (1) ◽  
pp. 104-109 ◽  
Author(s):  
Dominik Bender ◽  
Stephanie Tweer ◽  
Frank Werdin ◽  
Jens Rothenberger ◽  
Adrien Daigeler ◽  
...  
Keyword(s):  
Human Skin ◽  
Laser Doppler Flowmetry ◽  
Local Heating ◽  
Laser Doppler ◽  
Local Cooling ◽  
Skin Microcirculation ◽  
Doppler Flowmetry

scholarly journals Geldanamycin attenuates NO-mediated dilation in human skin

2002 ◽  
Vol 282 (1) ◽  
pp. H232-H236 ◽  
Author(s):  
Shubha Shastry ◽  
Michael J. Joyner
Keyword(s):  
Human Skin ◽  
Potential Role ◽  
Local Heating ◽  
Specific Inhibitor ◽  
Heat Shock Protein 90 ◽  
No Synthase ◽  
Vascular Conductance ◽  
Endothelial Nitric Oxide ◽  
Cutaneous Vascular Conductance ◽  
Cutaneous Blood

The binding of heat shock protein 90 (HSP90) to endothelial nitric oxide (NO) synthase (eNOS) can enhance eNOS activation. Studies have shown that the HSP90-specific inhibitor geldanamycin (GA) can cause attenuation of NO-mediated processes. Twenty subjects participated in one of two protocols. In each protocol, one forearm of each subject was instrumented with two intradermal microdialysis probes for drug delivery. Laser Doppler flowmeters were used to measure cutaneous blood flow. Skin sites were either treated with the endothelial agonist acetylcholine or locally heated to 42°C, a maneuver that evokes NO-mediated dilation. Interventions were performed with and without GA. In the presence of GA, maximal cutaneous vascular conductance (CVC) to ACh was 20 ± 3% lower than with ACh alone ( P < 0.001). During local heating, maximal CVC in the presence of GA was 22 ± 6% lower than during heating alone ( P < 0.01). The results show that GA can attenuate NO-mediated dilation in human skin, suggesting a potential role for HSP90 in activation of eNOS in the microcirculation.

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

2010 ◽  
Vol 298 (5) ◽  
pp. R1417-R1420 ◽  
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.

Bradykinin does not mediate cutaneous active vasodilation during heat stress in humans

2002 ◽  
Vol 93 (4) ◽  
pp. 1215-1221 ◽  
Author(s):  
D. L. Kellogg ◽  
Y. Liu ◽  
K. McAllister ◽  
C. Friel ◽  
P. E. Pérgola
Keyword(s):  
Blood Flow ◽  
Heat Stress ◽  
Receptor Antagonist ◽  
Healthy Subjects ◽  
Ringer Solution ◽  
Vascular Conductance ◽  
Doppler Flowmetry ◽  
Hoe 140 ◽  
Control Body ◽  
Cutaneous Vascular Conductance

To test the hypothesis that bradykinin effects cutaneous active vasodilation during hyperthermia, we examined whether the increase in skin blood flow (SkBF) during heat stress was affected by blockade of bradykinin B2 receptors with the receptor antagonist HOE-140. Two adjacent sites on the forearm were instrumented with intradermal microdialysis probes for local delivery of drugs in eight healthy subjects. HOE-140 was dissolved in Ringer solution (40 μM) and perfused at one site, whereas the second site was perfused with Ringer alone. SkBF was monitored by laser-Doppler flowmetry (LDF) at both sites. Mean arterial pressure (MAP) was monitored from a finger, and cutaneous vascular conductance (CVC) was calculated (CVC = LDF/MAP). Water-perfused suits were used to control body temperature and evoke hyperthermia. After hyperthermia, both microdialysis sites were perfused with 28 mM nitroprusside to effect maximal vasodilation. During hyperthermia, CVC increased at HOE-140 (69 ± 2% maximal CVC, P < 0.01) and untreated sites (65 ± 2% maximal CVC, P < 0.01). These responses did not differ between sites ( P > 0.05). Because the bradykinin B2-receptor antagonist HOE-140 did not alter SkBF responses to heat stress, we conclude that bradykinin does not mediate cutaneous active vasodilation.

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