Effects of 14 days of head-down tilt bed rest on cutaneous vasoconstrictor responses in humans

2003 ◽  
Vol 94 (6) ◽  
pp. 2113-2118 ◽  
Author(s):  
Thad E. Wilson ◽  
Manabu Shibasaki ◽  
Jian Cui ◽  
Benjamin D. Levine ◽  
Craig G. Crandall

This study tested the hypothesis that head-down tilt bed rest (HDBR) reduces adrenergic and nonadrenergic cutaneous vasoconstrictor responsiveness. Additionally, an exercise countermeasure group was included to identify whether exercise during bed rest might counteract any vasoconstrictor deficits that arose during HDBR. Twenty-two subjects underwent 14 days of strict 6° HDBR. Eight of these 22 subjects did not exercise during HDBR, while 14 of these subjects exercised on a supine cycle ergometer for 90 min a day at 75% of pre-bed rest heart rate maximum. To assess α-adrenergic vasoconstrictor responsiveness, intradermal microdialysis was used to locally administer norepinephrine (NE), while forearm skin blood flow (SkBF; laser-Doppler flowmetry) was monitored over microdialysis membranes. Nonlinear regression modeling was used to identify the effective drug concentration that caused 50% of the cutaneous vasoconstrictor response (EC50) and minimum values from the SkBF-NE dose-response curves. In addition, the effects of HDBR on nonadrenergic cutaneous vasoconstriction were assessed via the venoarteriolar response of the forearm and leg. HDBR did not alter EC50 or the magnitude of cutaneous vasoconstriction to exogenous NE administration regardless of whether the subjects exercised during HDBR. Moreover, HDBR did not alter the forearm venoarteriolar response in either the control or exercise groups during HDBR. However, HDBR significantly reduced the magnitude of cutaneous vasoconstriction due to the venoarteriolar response in the leg, and this response was similarly reduced in the exercise group. These data suggest that HDBR does not alter cutaneous vasoconstrictor responses to exogenous NE administration, whereas cutaneous vasoconstriction of the leg due to the venoarteriolar response is reduced after HDBR. It remains unclear whether attenuated venoarteriolar responses in the lower limbs contribute to reduced orthostatic tolerance after bed rest and spaceflight.

2007 ◽  
Vol 103 (6) ◽  
pp. 2026-2033 ◽  
Author(s):  
Fumio Yamazaki ◽  
Kazuo Takahara ◽  
Ryoko Sone ◽  
John M. Johnson

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.


2005 ◽  
Vol 288 (4) ◽  
pp. H1573-H1579 ◽  
Author(s):  
John M. Johnson ◽  
Tony C. Yen ◽  
Kun Zhao ◽  
Wojciech A. Kosiba

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.


2010 ◽  
Vol 298 (5) ◽  
pp. R1417-R1420 ◽  
Author(s):  
Jonathan E. Wingo ◽  
R. Matthew Brothers ◽  
Juan Del Coso ◽  
Craig G. Crandall

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.


2007 ◽  
Vol 293 (1) ◽  
pp. H30-H36 ◽  
Author(s):  
Caitlin S. Thompson-Torgerson ◽  
Lacy A. Holowatz ◽  
Nicholas A. Flavahan ◽  
W. Larry Kenney

Cutaneous vasoconstriction (VC), a critical thermoregulatory response to cold, is generally impaired with aging. However, the effects of aging on local cooling-induced VC and its underlying mechanisms are poorly understood. We tested whether aged skin exhibits attenuated localized cold-induced VC and whether Rho kinase-mediated cold-induced VC is augmented with age. Skin blood flow was monitored with laser Doppler flowmetry (LDF) on seven young and seven older subjects. Cutaneous vascular conductance (CVC; LDF/mean arterial pressure) was expressed as percentage change from baseline (%ΔCVCbase). In protocol 1, two forearm skin sites were cooled to six temperatures (31.5–19°C) for 10 min each or two temperatures (29°C, 24°C) for 30 min each, with no age differences in the magnitude of VC. In protocol 2, three forearm skin sites were instrumented for intradermal microdialysis and cooled to 24°C for 40 min. During minutes 1–5, there was no age difference in CVC responses at control sites (young: −45 ± 6% vs. older: −46 ± 3%, P > 0.9). Adrenoceptor antagonism (yohimbine + propranolol) abolished VC in young (to +15 ± 13%, P < 0.05) but only partially inhibited VC in older subjects (to −23 ± 6%, P < 0.05). Rho kinase inhibition plus adrenoceptor antagonism (yohimbine + propranolol + fasudil) abolished VC in both groups. During minutes 35–40, there was no age difference in control (young: −77 ± 4% vs. older: −70 ± 2%, P > 0.3) or adrenoceptor-antagonized responses (young: −61 ± 3% vs. older: −55 ± 2%, P > 0.3); however, Rho kinase inhibition plus adrenoceptor antagonism blocked more VC in older compared with young subjects (−19 ± 11% vs. −35 ± 3%, P < 0.05). Although its magnitude remains unaffected, cold-induced VC becomes less dependent on adrenergic and more dependent on Rho kinase signaling with advancing age.


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.


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.


2003 ◽  
Vol 94 (6) ◽  
pp. 2330-2336 ◽  
Author(s):  
C. G. Crandall ◽  
M. Shibasaki ◽  
T. E. Wilson ◽  
J. Cui ◽  
B. D. Levine

Cutaneous vasodilation and sweat rate are reduced during a thermal challenge after simulated and actual microgravity exposure. The effects of microgravity exposure on cutaneous vasodilator capacity and on sweat gland function are unknown. The purpose of this study was to test the hypothesis that simulated microgravity exposure, using the 6° head-down tilt (HDT) bed rest model, reduces maximal forearm cutaneous vascular conductance (FVC) and sweat gland function and that exercise during HDT preserves these responses. To test these hypotheses, 20 subjects were exposed to 14 days of strict HDT bed rest. Twelve of those subjects exercised (supine cycle ergometry) at 75% of pre-bed rest heart rate maximum for 90 min/day throughout HDT bed rest. Before and after HDT bed rest, maximal FVC was measured, via plethysmography, by heating the entire forearm to 42°C for 45 min. Sweat gland function was assessed by administering 1 × 10−6 to 2 M acetylcholine (9 doses) via intradermal microdialysis while simultaneously monitoring sweat rate over the microdialysis membranes. In the nonexercise group, maximal FVC and maximal stimulated sweat rate were significantly reduced after HDT bed rest. In contrast, these responses were unchanged in the exercise group. These data suggest that 14 days of simulated microgravity exposure, using the HDT bed rest model, reduces cutaneous vasodilator and sweating capacity, whereas aerobic exercise training during HDT bed rest preserves these responses.


2016 ◽  
Vol 39 (6) ◽  
pp. 204 ◽  
Author(s):  
Guy Amah ◽  
Sebastian Voicu ◽  
Philippe Bonnin ◽  
Nathalie Kubis

Purpose: We investigated whether forearm skin blood flow could be improved when a multilayer pulsatile inflatable suit was applied at a low pressure to the lower limbs and abdomen. We hypothesized that a non-invasive purely mechanical stimulation of the lower limbs could induce remote forearm blood flow modifications. Methods: The pulsatile suit induced a sequential compartmentalized low compression (65 mmHg), which was synchronized with each diastole of the cardiac cycle with each phase evolving centripetally (lower limbs to abdomen). Modifications of the forearm skin blood flow were continuously recorded by laser Doppler flowmetry (LDF) at baseline and during the pulsatile suit application. Endothelium-dependent and endothelium-independent vasodilations of the forearm skin microcirculation were measured by LDF in response to a local transdermal iontophoretic application of acetylcholine (ACh-test) and to hyperthermia (hyperT- test). Results: Twenty-four healthy volunteers, 12 men and 12 women (43±14 years) were included in the study. LDF responses increased 1) under pulsatile suit (97±106%, p


2012 ◽  
Vol 21 (3) ◽  
pp. 235-243 ◽  
Author(s):  
Derya Ozer Kaya ◽  
Irem Duzgun ◽  
Gul Baltaci ◽  
Selma Karacan ◽  
Filiz Colakoglu

Objective:To assess and compare the effects of 6 mo of Pilates and calisthenics on multijoint coordination and proprioception of the lower limbs at the 3rd and 6th mo of training.Design:Randomized, controlled, assessor-blinded, repeated-measures.Setting:University research laboratory.Participants and Intervention:Healthy, sedentary, female participants age 25–50 y were recruited and randomly divided into 3 groups: a calisthenic exercise group (n = 34, mean age ± SD 40 ± 8 y, body-mass index [BMI] 31.04 ± 4.83 kg/m2), a Pilates exercise group (n = 32, mean age ± SD 37 ± 8 y, BMI 31.04 ± 4.83 kg/m2), and a control group (n = 41, mean age ± SD 41 ± 7 y, BMI 27.09 ± 4.77 kg/m2). The calisthenics and Pilates groups underwent related training programs for 6 mo, while the controls had no specific training.Main Outcome Measures:Coordination and proprioception of the lower extremities with concentric and eccentric performances in the closed kinetic chain assessed with the monitored rehab functional squat system at baseline and at the 3rd and 6th mo of training.Results:For the within-group comparison, coordinative concentric and eccentric deviation values were significantly decreased for both dominant and nondominant lower limbs at pretraining and at the 3rd and 6th mo posttraining in the calisthenics group (P < .05). In contrast, there was no improvement in the Pilates group throughout the training. However, for comparisons between groups, the baseline values of coordinative concentric and eccentric deviations were different in the calisthenics group than in Pilates and the controls (P < .05). There were no differences in the proprioception values of either visible or nonvisible movement in any group throughout the training (P > .05).Conclusions:It seems that calisthenic exercises are more likely to improve coordination of the lower extremity after 3 and 6 mo of training than Pilates exercises. Calisthenic exercises may be useful for individuals who require improved coordination.


2003 ◽  
Vol 284 (5) ◽  
pp. H1662-H1667 ◽  
Author(s):  
Lacy A. Holowatz ◽  
Belinda L. Houghton ◽  
Brett J. Wong ◽  
Brad W. Wilkins ◽  
Aaron W. Harding ◽  
...  

Thermoregulatory cutaneous vasodilation is diminished in the elderly. The goal of this study was to test the hypothesis that a reduction in nitric oxide (NO)-dependent mechanisms contributes to the attenuated reflex cutaneous vasodilation in older subjects. Seven young (23 ± 2 yr) and seven older (71 ± 6 yr) men were instrumented with two microdialysis fibers in the forearm skin. One site served as control (Ringer infusion), and the second site was perfused with 10 mM N G-nitro-l-arginine methyl ester to inhibit NO synthase (NOS) throughout the protocol. Water-perfused suits were used to raise core temperature 1.0°C. Red blood cell (RBC) flux was measured with laser-Doppler flowmetry over each microdialysis fiber. Cutaneous vascular conductance (CVC) was calculated as RBC flux per mean arterial pressure, with values expressed as a percentage of maximal vasodilation (infusion of 28 mM sodium nitroprusside). NOS inhibition reduced CVC from 75 ± 6% maximal CVC (CVCmax) to 53 ± 3% CVCmax in the young subjects and from 64 ± 5% CVCmax to 29 ± 2% CVCmax in the older subjects with a 1.0°C rise in core temperature. Thus the relative NO-dependent portion of cutaneous active vasodilation (AVD) accounted for ∼23% of vasodilation in the young subjects and 60% of the vasodilation in the older subjects at this level of hyperthermia ( P < 0.001). In summary, NO-mediated pathways contributed more to the total vasodilatory response of the older subjects at high core temperatures. This suggests that attenuated cutaneous vasodilation with age may be due to a reduction in, or decreased vascular responsiveness to, the unknown neurotransmitter(s) mediating AVD.


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