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

2011 ◽  
Vol 111 (1) ◽  
pp. 170-176 ◽  
Author(s):  
Fumio Yamazaki ◽  
Nagisa Yuge

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.

2012 ◽  
Vol 112 (10) ◽  
pp. 1689-1697 ◽  
Author(s):  
Fumio Yamazaki

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.


2005 ◽  
Vol 288 (4) ◽  
pp. F771-F777 ◽  
Author(s):  
David M. Pollock ◽  
John M. Jenkins ◽  
Anthony K. Cook ◽  
John D. Imig ◽  
Edward W. Inscho

The signaling pathways of endothelin (ET)-1-mediated vasoconstriction in the renal circulation have not been elucidated but appear to be distinct between ETA and ETB receptors. The purpose of this study was to determine the role of L-type Ca2+ channels in the vasoconstrictor response to ET-1 and the ETB receptor agonist sarafotoxin 6c (S6c) in the rat kidney. Renal blood flow (RBF) was measured with an ultrasonic flow probe in anesthetized rats, and a microcatheter was inserted into the renal artery for drug infusion. All rats were given vehicle (0.9% NaCl) or three successive bolus injections (1, 10, and 100 pmol) of ET-1 or S6c at 30-min intervals ( n = 6 in each group). ET-1 and S6c produced dose-dependent decreases in RBF. The Ca2+ channel blocker nifedipine (1.5 μg) significantly attenuated the RBF response only at the highest doses of ET-1 and S6c. In the isolated blood-perfused juxtamedullary nephron preparation, Ca2+ channel blockade with diltiazem had a very small inhibitory effect on ET-1-induced decreases in afferent arteriolar diameter only at the lowest concentrations of ET-1. In vascular smooth muscle cells isolated from preglomerular vessels, ET-1 produced a typical biphasic Ca2+ response, whereas S6c had no effect on cytosolic Ca2+. Furthermore, Ca2+ channel blockade (diltiazem or Ni2+) had no effect on the peak or sustained increase in cytosolic Ca2+ produced by ET-1. These results support the hypothesis that L-type Ca2+ channels play only a minor role in the constrictor responses to ET-1 in the renal microcirculation.


2002 ◽  
Vol 93 (4) ◽  
pp. 1215-1221 ◽  
Author(s):  
D. L. Kellogg ◽  
Y. Liu ◽  
K. McAllister ◽  
C. Friel ◽  
P. E. Pérgola

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.


1999 ◽  
Vol 87 (1) ◽  
pp. 381-385 ◽  
Author(s):  
Nisha Charkoudian ◽  
John M. Johnson

To determine whether cardiovascular influences of exogenous female steroid hormones include effects on reflex thermoregulatory control of the adrenergic cutaneous vasoconstrictor system, we conducted ramp decreases in skin temperature (Tsk) in eight women in both high- and low (placebo)-progesterone/estrogen phases of oral contraceptive use. With the use of water-perfused suits, Tsk was held at 36°C for 10 min (to minimize initial vasoconstrictor activity) and was then decreased in a ramp, ∼0.2°C/min for 12–15 min. Subjects rested supine for 30–40 min before each experiment, and the protocol was terminated before the onset of shivering. Skin blood flow was monitored by laser-Doppler flowmetry and arterial pressure by finger photoplethysmography. In all experiments, cutaneous vasoconstriction began immediately with the onset of cooling, and cutaneous vascular conductance (CVC) decreased progressively with decreasing Tsk. Regression analysis of the relationship of CVC to Tsk showed no difference in slope between phases (low-hormone phase: 17.67 ± 5.57; high-hormone phase: 17.40 ± 8.00 %baseline/°C; P > 0.05). Additional studies involving local blockade confirmed this response as being solely due to the adrenergic vasoconstrictor system. Waking oral temperature (Tor) was significantly higher on high-hormone vs. low-hormone days (36.60 ± 0.11 vs. 36.37 ± 0.09 °C, respectively; P < 0.02). Integrative analysis of CVC in terms of simultaneous values for Tsk and Tor showed that the cutaneous vasoconstrictor response was shifted in the high-hormone phase such that a higher Tor was maintained throughout cooling ( P < 0.05). Thus reflex thermoregulatory control of the cutaneous vasoconstrictor system is shifted to higher internal temperatures by exogenous female reproductive hormones.


1999 ◽  
Vol 86 (5) ◽  
pp. 1676-1686 ◽  
Author(s):  
Carla M. Thomas ◽  
Jane M. Pierzga ◽  
W. Larry Kenney

To determine the effect and underlying mechanisms of exercise training and the influence of age on the skin blood flow (SkBF) response to exercise in a hot environment, 22 young (Y; 18–30 yr) and 21 older (O; 61–78 yr) men were assigned to 16 wk of aerobic (A; YA, n = 8; OA, n = 11), resistance (R; YR, n = 7; OR, n = 3), or no training (C; YC, n = 7; OC, n = 7). Before and after treatment, subjects exercised at 60% of maximum oxygen consumption (V˙o 2 max) on a cycle ergometer for 60 min at 36°C. Cutaneous vascular conductance, defined as SkBF divided by mean arterial pressure, was monitored at control (vasoconstriction intact) and bretylium-treated (vasoconstriction blocked) sites on the forearm using laser-Doppler flowmetry. Forearm vascular conductance was calculated as forearm blood flow (venous occlusion plethysmography) divided by mean arterial pressure. Esophageal and skin temperatures were recorded. Only aerobic training (functionally defined a priori as a 5% or greater increase inV˙o 2 max) produced a decrease in the mean body temperature threshold for increasing forearm vascular conductance (36.89 ± 0.08 to 36.63 ± 0.08°C, P < 0.003) and cutaneous vascular conductance (36.91 ± 0.08 to 36.65 ± 0.08°C, P < 0.004). Similar thresholds between control and bretylium-treated sites indicated that the decrease was mediated through the active vasodilator system. This shift was more pronounced in the older men who presented greater training-induced increases in V˙o 2 maxthan did the young men (22 and 9%, respectively). In summary, older men improved their SkBF response to exercise-heat stress through the effect of aerobic training on the cutaneous vasodilator system.


1998 ◽  
Vol 85 (3) ◽  
pp. 824-829 ◽  
Author(s):  
D. L. Kellogg ◽  
C. G. Crandall ◽  
Y. Liu ◽  
N. Charkoudian ◽  
J. M. Johnson

Whether nitric oxide (NO) is involved in cutaneous active vasodilation during hyperthermia in humans is unclear. We tested for a role of NO in this process during heat stress (water-perfused suits) in seven healthy subjects. Two forearm sites were instrumented with intradermal microdialysis probes. One site was perfused with the NO synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME) dissolved in Ringer solution to abolish NO production. The other site was perfused with Ringer solution only. At those sites, skin blood flow (laser-Doppler flowmetry) and sweat rate were simultaneously and continuously monitored. Cutaneous vascular conductance, calculated from laser-Doppler flowmetry and mean arterial pressure, was normalized to maximal levels as achieved by perfusion with the NO donor nitroprusside through the microdialysis probes. Under normothermic conditions,l-NAME did not significantly reduce cutaneous vascular conductance. During hyperthermia, with skin temperature held at 38–38.5°C, internal temperature rose from 36.66 ± 0.10 to 37.34 ± 0.06°C ( P < 0.01). Cutaneous vascular conductance at untreated sites increased from 12 ± 2 to 44 ± 5% of maximum, but only rose from 13 ± 2 to 30 ± 5% of maximum at l-NAME-treated sites ( P < 0.05 between sites) during heat stress. l-NAME had no effect on sweat rate ( P > 0.05). Thus cutaneous active vasodilation requires functional NO synthase to achieve full expression.


2016 ◽  
Vol 41 (8) ◽  
pp. 879-887 ◽  
Author(s):  
Nicole E. Moyen ◽  
Jenna M. Burchfield ◽  
Cory L. Butts ◽  
Jordan M. Glenn ◽  
Matthew A. Tucker ◽  
...  

The purpose of this study was to evaluate the effect of obesity and mild hypohydration on local sweating (LSR) and cutaneous vascular conductance (CVC) responses during passive heat stress in females. Thirteen obese (age, 24 ± 4 years; 45.4% ± 5.2% body fat) and 12 nonobese (age, 22 ± 2 years; 25.1% ± 3.9% body fat) females were passively heated (1.0 °C rectal temperature increase) while either euhydrated (EUHY) or mildly hypohydrated (HYPO; via fluid restriction). Chest and forearm LSR (ventilated capsule) and CVC (Laser Doppler flowmetry) onset, sensitivity, and plateau/steady state were recorded as mean body temperature increased (ΔTb). Participants began trials EUHY (urine specific gravity, Usg = 1.009 ± 0.006) or HYPO (Usg = 1.025 ± 0.004; p < 0.05), and remained EUHY or HYPO. Independent of obesity, HYPO decreased sweat sensitivity at the chest (HYPO = 0.79 ± 0.35, EUHY = 0.95 ± 0.39 Δmg·min−1·cm−2/°C ΔTb) and forearm (HYPO = 0.82 ± 0.39, EUHY = 1.06 ± 0.34 Δmg·min−1·cm−2/°C ΔTb); forearm LSR plateau was also decreased (HYPO = 0.66 ± 0.19, EUHY = 0.78 ± 0.23 mg·min−1·cm−2; all p < 0.05). Overall, obese females had lower chest-sweat sensitivity (0.72 ± 0.35 vs. 1.01 ± 0.33 Δmg·min−1·cm−2/°C ΔTb) and plateau (0.55 ± 0.27 vs. 0.80 ± 0.25 mg·min−1·cm−2; p < 0.05). While hypohydrated, obese females had a lower chest LSR (p < 0.05) versus nonobese females midway (0.45 ± 0.26 vs. 0.73 ± 0.23 mg·min−1·cm−2) and at the end (0.53 ± 0.27 vs. 0.81 ± 0.24 mg·min−1·cm−2) of heating. Furthermore, HYPO (relative to the EUHY trials) led to a greater decrease in CVC sensitivity in obese (–28 ± 27 Δ% maximal CVC/°C ΔTb) versus nonobese females (+9.2 ± 33 Δ% maximal CVC/°C ΔTb; p < 0.05). In conclusion, mild hypohydration impairs females’ sweating responses during passive heat stress, and this effect is exacerbated when obese.


2007 ◽  
Vol 103 (3) ◽  
pp. 963-968 ◽  
Author(s):  
D. L. Kellogg ◽  
G. J. Hodges ◽  
C. R. Orozco ◽  
T. M. Phillips ◽  
J. L. Zhao ◽  
...  

To test the hypothesis that cutaneous active vasodilation in heat stress is mediated by a redundant cholinergic cotransmitter system, we examined the effects of atropine on skin blood flow (SkBF) increases during heat stress in persons with (CF) and without cystic fibrosis (non-CF). Vasoactive intestinal peptide (VIP) has been implicated as a mediator of cutaneous vasodilation in heat stress. VIP-containing cutaneous neurons are sparse in CF, yet SkBF increases during heat stress are normal. In CF, augmented ACh release or muscarinic receptor sensitivity could compensate for decreased VIP; if so, active vasodilation would be attenuated by atropine in CF relative to non-CF. Atropine was administered into skin by iontophoresis in seven CF and seven matched non-CF subjects. SkBF was monitored by laser-Doppler flowmetry (LDF) at atropine treated and untreated sites. Blood pressure [mean arterial pressure (MAP)] was monitored (Finapres), and cutaneous vascular conductance was calculated (CVC = LDF/MAP). The protocol began with a normothermic period followed by a 3-min cold stress and 30–45 min of heat stress. Finally, LDF sites were warmed to 42°C to effect maximal vasodilation. CVC was normalized to its site-specific maximum. During heat stress, CVC increased in both CF and non-CF ( P < 0.01). CVC increases were attenuated by atropine in both groups ( P < 0.01); however, the responses did not differ between groups ( P = 0.99). We conclude that in CF there is not greater dependence on redundant cholinergic mechanisms for cutaneous active vasodilation than in non-CF.


1993 ◽  
Vol 264 (3) ◽  
pp. E398-E402 ◽  
Author(s):  
M. Dey ◽  
M. Michalkiewicz ◽  
L. J. Huffman ◽  
G. A. Hedge

It has been suggested that thyroid blood flow (TBF) is regulated by both parasympathetic and sympathetic nerves. Because thyroxine (T4) pretreatment increases the sensitivity of the thyroid to the effects of thyrotropin, the present study was conducted to determine whether T4 pretreatment can also sensitize the thyroid to the effect of parasympathetic stimulation on TBF. Untreated or T4-pretreated rats were anesthetized, and both superior laryngeal nerves (SLN) were transected. TBF was continuously monitored by laser Doppler flowmetry (LDF), and thyroid vascular conductance (TVC) was also determined by the microsphere technique. Stimulation of the SLN had no effect on TBF or TVC in untreated rats when measured by LDF or microspheres. In contrast, stimulation of the SLN after T4 pretreatment increased TBF by 65 +/- 21% over prestimulus levels as measured by LDF. TVC was also increased significantly (P < 0.05) in these rats compared with TVC in a nonstimulated T4-pretreated group. To examine the role of muscarinic receptor activation in the mediation of these increases in TVC, T4 pretreated rats were given saline or atropine prior to SLN transection. Stimulation of the SLN in T4-pretreated rats given saline increased TVC significantly (P < 0.05) compared with TVC in the nonstimulated saline-treated or atropine-treated group. In contrast, TVC in the stimulated group given saline was not significantly different from the group that was stimulated after atropine injection. Our results suggest that the thyroidal vascular responsiveness to parasympathetic stimulation is increased in the hyperthyroid condition.


2003 ◽  
Vol 94 (3) ◽  
pp. 930-934 ◽  
Author(s):  
Ken Aoki ◽  
Dan P. Stephens ◽  
Adham R. Saad ◽  
John M. Johnson

To test for a diurnal difference in the vasoconstrictor control of the cutaneous circulation, we performed whole body skin cooling (water-perfused suits) at 0600 (AM) and 1600 (PM). After whole body skin temperature (Tsk) was controlled at 35°C for 10 min, it was progressively lowered to 32°C over 18–20 min. Skin blood flow (SkBF) was monitored by laser-Doppler flowmetry at three control sites and at a site that had been pretreated with bretylium by iontophoresis to block noradrenergic vasoconstriction. After whole body skin cooling, maximal cutaneous vascular conductance (CVC) was measured by locally warming the sites of SkBF measurement to 42°C for 30 min. Before whole body skin cooling, sublingual temperature (Tor) in the PM was significantly higher than that in the AM ( P < 0.05), but CVC, expressed as a percentage of maximal CVC (%CVCmax), was not statistically different between AM and PM. During whole body skin cooling, %CVCmax levels at bretylium-treated sites in AM or PM were not significantly reduced from baseline. In the PM, %CVCmax at control sites fell significantly at Tsk of 34.3 ± 0.01°C and lower ( P< 0.05). In contrast, in the AM %CVCmax at control sites was not significantly reduced from baseline until Tskreached 32.3 ± 0.01°C and lower ( P < 0.05). Furthermore, the decrease in %CVCmax in the PM was significantly greater than that in AM at Tsk of 33.3 ± 0.01°C and lower ( P < 0.05). Integrative analysis of the CVC response with respect to both Tor and Tsk showed that the cutaneous vasoconstrictor response was shifted to higher internal temperatures in the PM. These findings suggest that during whole body skin cooling the reflex control of the cutaneous vasoconstrictor system is shifted to a higher internal temperature in the PM. Furthermore, the slope of the relationship between CVC and Tsk is steeper in the PM compared with that in the AM.


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