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.

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

2007 ◽  
Vol 292 (4) ◽  
pp. H1700-H1705 ◽  
Author(s):  
Caitlin S. Thompson-Torgerson ◽  
Lacy A. Holowatz ◽  
Nicholas A. Flavahan ◽  
W. Larry Kenney
Keyword(s):  
Laser Doppler Flowmetry ◽  
Combined Treatment ◽  
Rho Kinase ◽  
Laser Doppler ◽  
Whole Body ◽  
Local Skin ◽  
Doppler Flowmetry ◽  
Thermoregulatory Model ◽  
Cutaneous Vasoconstriction

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.

Role of sympathetic nerves in the vascular effects of local temperature in human forearm skin

1993 ◽  
Vol 265 (3) ◽  
pp. H785-H792 ◽  
Author(s):  
P. E. Pergola ◽  
D. L. Kellogg ◽  
J. M. Johnson ◽  
W. A. Kosiba ◽  
D. E. Solomon
Keyword(s):  
Skin Temperature ◽  
Whole Body ◽  
Adrenergic Nerve ◽  
Local Cooling ◽  
Local Skin ◽  
Doppler Flowmetry ◽  
Human Forearm ◽  
Forearm Skin ◽  
Local Warming

The role of adrenergic nerve function in the cutaneous vascular response to changes in local skin temperature in the human forearm was examined using three protocols: 1) blocking release of norepinephrine presynaptically by local iontophoresis of bretylium (BT), 2) altering background adrenergic tone by changing whole body skin temperature, and 3) blocking cutaneous nerves by proximal infiltration of local anesthetic. Forearm skin blood flow was measured by laser-Doppler flowmetry (LDF) and cutaneous vascular conductance (CVC) was calculated as LDF/blood pressure. In protocol 1, local cooling (29 degrees C) elicited a rapid and sustained fall in CVC at control sites (-43 +/- 8%) in contrast to a biphasic response at BT-treated sites, consisting of an initial vasodilation followed by a vasoconstriction (percent change CVC = 28 +/- 13 and -34 +/- 18, respectively). Local warming (39 degrees C) increased CVC at control and at BT-treated sites by 331 +/- 46 and 139 +/- 31%, respectively. In protocol 2, at a neutral, cool, or warm whole body skin temperature, local cooling (29 degrees C) elicited similar reductions in CVC (-34 +/- 8, -29 +/- 5, and -30 +/- 4%, respectively), and local warming (38 degrees C) produced similar increases in CVC (89 +/- 15, 85 +/- 21, and 74 +/- 22%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Sympathetic nonnoradrenergic cutaneous vasoconstriction in women is associated with reproductive hormone status

2002 ◽  
Vol 282 (1) ◽  
pp. H264-H272 ◽  
Author(s):  
Dan P. Stephens ◽  
Lee Ann T. Bennett ◽  
Ken Aoki ◽  
Wojciech A. Kosiba ◽  
Nisha Charkoudian ◽  
...  
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Contraceptive Use ◽  
Intradermal Injection ◽  
Reproductive Hormones ◽  
Whole Body ◽  
Reproductive Hormone ◽  
Doppler Flowmetry ◽  
Hormone Status ◽  
Cutaneous Vasoconstriction

We tested whether a nonnoradrenergic component of reflex vasoconstriction of skin blood flow (SkBF) is sensitive to female reproductive hormones. Six women taking oral contraceptives underwent whole-body cooling during high-hormone (HH) and low-hormone (LH) phases of oral contraceptive use. SkBF was monitored by laser Doppler flowmetry (LDF) at sites treated by intradermal injection of yohimbine-propranolol (5 mM and 1 mM; YOPR) to block the effects of norepinephrine (NE) or at saline (Sal) control sites. Mean arterial pressure (MAP) was measured with the use of the Penaz method. Cutaneous vascular conductance (CVC = LDF/mean arterial pressure) was expressed as a percentage of baseline. Whole body skin temperature was decreased from 34 to 31°C in HH and LH. In both HH and LH, CVC at Sal-treated sites was reduced during cooling (CVC = 53.1 ± 8.6% and 54.4 ± 4.2%, both P < 0.05). In HH, CVC at YOPR sites was reduced during cooling (78.8 ± 3.6%, P < 0.05). In contrast, CVC at YOPR sites was not reduced significantly during cooling in LH (CVC = 95.9 ± 2.8%, P > 0.05). Across phases, CVC at YOPR sites during cooling was significantly different ( P < 0.05). After cooling, the effects of NE at YOPR sites were completely blocked. These data indicate that a nonnoradrenergic mechanism of reflex cutaneous vasoconstriction is present in women and is associated with reproductive hormone status.

scholarly journals Roles of nitric oxide synthase isoforms in cutaneous vasodilation induced by local warming of the skin and whole body heat stress in humans

2009 ◽  
Vol 107 (5) ◽  
pp. 1438-1444 ◽  
Author(s):  
Dean L. Kellogg ◽  
Joan L. Zhao ◽  
Yubo Wu
Keyword(s):  
Nitric Oxide ◽  
Heat Stress ◽  
No Synthase ◽  
Whole Body ◽  
Doppler Flowmetry ◽  
Vasodilator Response ◽  
Cutaneous Vasodilation ◽  
Forearm Skin ◽  
Whole Body Heat Stress ◽  
Body Heat

Nitric oxide (NO) participates in the cutaneous vasodilation caused by increased local skin temperature (Tloc) and whole body heat stress in humans. In forearm skin, endothelial NO synthase (eNOS) participates in vasodilation due to elevated Tloc and neuronal NO synthase (nNOS) participates in vasodilation due to heat stress. To explore the relative roles and interactions of these isoforms, we examined the effects of a relatively specific eNOS inhibitor, Nω-amino-l-arginine (LNAA), and a specific nNOS inhibitor, Nω-propyl-l-arginine (NPLA), both separately and in combination, on skin blood flow (SkBF) responses to increased Tloc and heat stress in two protocols. In each protocol, SkBF was monitored by laser-Doppler flowmetry (LDF) and mean arterial pressure (MAP) by Finapres. Cutaneous vascular conductance (CVC) was calculated (CVC = LDF/MAP). Intradermal microdialysis was used to treat one site with 5 mM LNAA, another with 5 mM NPLA, a third with combined 5 mM LNAA and 5 mM NPLA (Mix), and a fourth site with Ringer only. In protocol 1, Tloc was controlled with combined LDF/local heating units. Tloc was increased from 34°C to 41.5°C to cause local vasodilation. In protocol 2, after a period of normothermia, whole body heat stress was induced (water-perfused suits). At the end of each protocol, all sites were perfused with 58 mM nitroprusside to effect maximal vasodilation for data normalization. In protocol 1, at Tloc = 34°C, CVC did not differ between sites ( P > 0.05). LNAA and Mix attenuated CVC increases at Tloc = 41.5°C to similar extents ( P < 0.05, LNAA or Mix vs. untreated or NPLA). In protocol 2, in normothermia, CVC did not differ between sites ( P > 0.05). During heat stress, NPLA and Mix attenuated CVC increases to similar extents, but no significant attenuation occurred with LNAA ( P < 0.05, NPLA or Mix vs. untreated or LNAA). In forearm skin, eNOS mediates the vasodilator response to increased Tloc and nNOS mediates the vasodilator response to heat stress. The two isoforms do not appear to interact during either response.

scholarly journals Local tetrahydrobiopterin administration augments reflex cutaneous vasodilation through nitric oxide-dependent mechanisms in aged human skin

2012 ◽  
Vol 112 (5) ◽  
pp. 791-797 ◽  
Author(s):  
Anna E. Stanhewicz ◽  
Rebecca S. Bruning ◽  
Caroline J. Smith ◽  
W. Larry Kenney ◽  
Lacy A. Holowatz
Keyword(s):  
Nitric Oxide ◽  
Human Skin ◽  
Oxidant Stress ◽  
Local Heat ◽  
Whole Body ◽  
Mean Body Temperature ◽  
Doppler Flowmetry ◽  
Cutaneous Vasodilation ◽  
Aged Skin ◽  
Reflex Cutaneous Vasodilation

Functional constitutive nitric oxide synthase (NOS) is required for full expression of reflex cutaneous vasodilation that is attenuated in aged skin. Both the essential cofactor tetrahydrobiopterin (BH4) and adequate substrate concentrations are necessary for the functional synthesis of nitric oxide (NO) through NOS, both of which are reduced in aged vasculature through increased oxidant stress and upregulated arginase, respectively. We hypothesized that acute local BH4 administration or arginase inhibition would similarly augment reflex vasodilation in aged skin during passive whole body heat stress. Four intradermal microdialysis fibers were placed in the forearm skin of 11 young (22 ± 1 yr) and 11 older (73 ± 2 yr) men and women for local infusion of 1) lactated Ringer, 2) 10 mM BH4, 3) 5 mM ( S)-(2-boronoethyl)-l-cysteine + 5 mM Nω-hydroxy-nor-l-arginine to inhibit arginase, and 4) 20 mM NG-nitro-l-arginine methyl ester (l-NAME) to inhibit NOS. Red cell flux was measured at each site by laser-Doppler flowmetry (LDF) as reflex vasodilation was induced. After a 1.0°C rise in oral temperature (Tor), mean body temperature was clamped and 20 mM l-NAME was perfused at each site. Cutaneous vascular conductance was calculated (CVC = LDF/mean arterial pressure) and expressed as a percentage of maximum (%CVCmax; 28 mM sodium nitroprusside and local heat, 43°C). Vasodilation was attenuated at the control site of the older subjects compared with young beginning at a 0.3°C rise in Tor. BH4 and arginase inhibition both increased vasodilation in older (BH4: 55 ± 5%; arginase-inhibited: 47 ± 5% vs. control: 37 ± 3%, both P < 0.01) but not young subjects compared with control (BH4: 51 ± 4%CVCmax; arginase-inhibited: 55 ± 4%CVCmax vs. control: 56 ± 6%CVCmax, both P > 0.05) at a 1°C rise in Tor. With a 1°C rise in Tor, local BH4 increased NO-dependent vasodilation in the older (BH4: 31.8 ± 2.4%CVCmax vs. control: 11.7 ± 2.0%CVCmax, P < 0.001) but not the young (BH4: 23 ± 4%CVCmax vs. control: 21 ± 4%CVCmax, P = 0.718) subject group. Together these data suggest that reduced BH4 contributes to attenuated vasodilation in aged human skin and that BH4 NOS coupling mechanisms may be a potential therapeutic target for increasing skin blood flow during hyperthermia in older humans.

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

Peripheral Blood Perfusion Correlates with Microvascular Abnormalities in Systemic Sclerosis: A Laser-Doppler and Nailfold Videocapillaroscopy Study

2010 ◽  
Vol 37 (6) ◽  
pp. 1174-1180 ◽  
Author(s):  
MAURIZIO CUTOLO ◽  
CARMELA FERRONE ◽  
CARMEN PIZZORNI ◽  
STEFANO SOLDANO ◽  
BRUNO SERIOLO ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Negative Correlation ◽  
Healthy Subjects ◽  
Blood Perfusion ◽  
Laser Doppler ◽  
Nailfold Videocapillaroscopy ◽  
Microvascular Damage ◽  
Local Skin ◽  
Doppler Flowmetry ◽  
Prostacyclin Analog

Objective.To investigate possible correlations between fingertip blood perfusion (FBP) status, assessed by laser Doppler flowmetry (LDF), and morphological microvascular abnormalities, detected by nailfold videocapillaroscopy (NVC), in patients with systemic sclerosis (SSc). The effects on FBP of intravenous (IV) treatment with the prostacyclin analog iloprost were also investigated.Methods.Thirty-four consecutive patients with SSc and 16 healthy subjects were evaluated. LDF was performed by analyzing blood perfusion at the fingertips in both hands. Patients with SSc were distributed into the appropriate NVC pattern of microangiopathy (early, active, and late). Iloprost was administered to inpatients with SSc by 24-hour IV infusion for 7 consecutive days (4 μg/h).Results.FBP was significantly lower in patients with SSc (p < 0.05) compared to controls. Heating of the LDF probe at 36°C induced a significant increase of FBP in all subjects (p < 0.001), but the slope of variation was significantly lower in patients with SSc compared to controls (p < 0.05). Patients with SSc showing the late NVC pattern of microangiopathy had significantly lower FBP than patients with the active and early NVC patterns (p < 0.05). A negative correlation was observed between FBP and NVC rating of the microvascular damage (p < 0.05). After iloprost treatment, a significant increase of FBP was observed in patients with SSc (p < 0.05).Conclusion.Patients with SSc show a decreased FBP partially reversible by local skin heating. The FBP correlated negatively with the extent of nailfold microvascular damage, and IV iloprost treatment increased the FBP.

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