Reduction In Cutaneous Vascular Conductance Research Articles

Acute effects of energy drink consumption on microvascular reactivity in young male volunteers at rest: a randomized trial.

Energy drinks are nonalcoholic beverages whose main ingredients are sugar, taurine, and caffeine. The consumption of energy drinks is increasing worldwide, but only a few conflicting studies have investigated the vascular effects of energy drinks in young adults. The aim of this study was to evaluate microvascular reactivity before and after energy drinks consumption in young healthy male volunteers. This was a cross-sectional prospective study. Microvascular reactivity signals were evaluated in the skin of the forearm using laser speckle contrast imaging with acetylcholine (ACh) iontophoresis before and 90 and 180 min after the randomized consumption of one ED or the same volume of water (control), followed by a postocclusive reactive hyperemia (PORH) test. Thirty-two volunteers were evaluated (age: 25.4±4.3 years). Energy drink consumption prevented the rest-induced reduction in cutaneous vascular conductance over time that was observed in the control group. In the control group, there were significant reductions in microvascular vasodilation at 90 and 180 min compared to baseline (P=0.004), but this was not the case in the energy drink group (P=0.76). Our results demonstrated that the reduction in microvascular conductance associated with prolonged immobility can be prevented by the consumption of one energy drink, highlighting the vasodilator effects of this beverage in young individuals at rest. The between-study variability in terms of the brand of energy drinks and the ingested volume, as well as the method of vascular evaluation and the inclusion criteria, may explain the discrepancies among previous studies on the vascular effects of energy drinks.

Intradermal Administration of Atrial Natriuretic Peptide Attenuates Cutaneous Vasodilation but Not Sweating in Young Men during Exercise in the Heat

Introduction: Prolonged exercise in the heat stimulates plasma release of atrial natriuretic peptide (ANP) in association with dehydration-induced reductions in blood volume. Elevated plasma ANP levels under these conditions may indirectly attenuate cutaneous blood flow and sweating responses due to the effects of this hormone on central blood volume and plasma osmolality and the resulting stimulation of nonthermal reflexes. However, it remains unclear whether cutaneous blood flow and sweating are directly modulated by ANP at the level of the cutaneous end organs (cutaneous microvessels and eccrine sweat glands) during prolonged exercise in the heat. Objective: Therefore, we evaluated the effects of local ANP administration on forearm cutaneous vascular conductance (CVC) and local sweat rate (LSR) during rest and exercise in the heat. Methods: In 9 habitually active young men (26 ± 6 years) CVC and LSR were evaluated at 3 intradermal microdialysis sites continuously perfused with lactated Ringer solution (control) or ANP (0.1 or 1.0 μM). Participants rested in a non-heat-stress condition (25°C) for approximately 60 min followed by 70 min in the heat (35°C). They then performed 50 min of moderate-intensity cycling (approx. 55% VO_{2 peak}), with a 30-min recovery. Thereafter, 50 mM sodium nitroprusside was administered at all sites to elicit maximum CVC, which was subsequently used to normalize all values (CVC_%max). Results: No effects of ANP on CVC_%max were observed in the non-heat-stress resting condition compared to the untreated control site (both p > 0.05). Conversely during rest in the heat there was an 11% (5–17%) reduction in CVC_%max at the 1.0 μM ANP site relative to the untreated control site (p < 0.05). At the end of exercise CVC_%max was attenuated by 12% (1–23%) at the 0.1 μM ANP site and by 21% (7–35%) at the 1.0 μM ANP site relative to the untreated control site (all p < 0.05). Conversely, neither concentration of ANP influenced sweating at any time point (all p > 0.05). Conclusion: Intradermal ANP administration directly attenuated cutaneous blood flow, but not sweating, in habitually active young men during rest and exercise in the heat.

Exaggerated Alpha‐1 Adrenoreceptor Mediated Vasoconstriction in Young Black Men is not Influenced by Superoxide‐Mediated Oxidative Stress

Black individuals (BL) have a greater risk for hypertension and cardiovascular disease than other populations, the cause of which is likely multifactorial. However, vascular dysfunction appears to be a key preceding factor to the racial disparities observed. This observation has been demonstrated in young, otherwise healthy BL. Our group recently demonstrated that young BL men (BM) exhibit exaggerated sympathetic vascular transduction (SVT), i.e., greater vasoconstriction and pressor responses to spontaneous bursts of sympathetic nerve activity, at rest compared to young white men (WM). This response may be mediated by elevated oxidative stress, which may be 1) reducing nitric oxide (NO) bioavailability and subsequent vasodilatory capacity and/or 2) directly affecting blood vessel reactivity. In this regard, previous literature has established that young BM have elevated oxidative stress and reduced NO bioavailability relative to other populations. Whether these conditions contribute to increased SVT in BM is currently unknown. Accordingly, this study tested the hypothesis that BM have an exaggerated vasoconstrictor response to the selective α1‐adrenoreceptor agonist phenylephrine (PE) compared to WM which is augmented by elevated oxidative stress. To test this hypothesis, four intradermal microdialysis membranes were placed in the dorsal forearm of 3 WM and 6 BM (mean ± SD; age: 24±5 vs. 22±3 y) and the skin blood flow (SkBF) responses to intradermal infusion of PE were assessed. Following trauma resolution, each site received one of four infusions for 30‐min: lactated Ringer's (control), apocynin (NADPH oxidase inhibitor; 100 μM), allopurinol (xanthine oxidase inhibitor; 10 μM), or tempol (superoxide scavenger; 10 μM). Each site was then locally heated to 33°C for 10‐min to establish baseline SkBF. Each site then received a coinfusion of PE (100 mM) for 6‐min to elicit vasoconstriction, with the response presented as a percent reduction in cutaneous vascular conductance (CVC; flux/mean arterial pressure) from baseline (%CVCB). Following PE administration, BM exhibited exaggerated vasoconstriction compared to WM (control: −69.0±16.5 vs. −34.8±15.2 %CVCB; apocynin: −58.1±18.3 vs. −43.5± 2.4 %CVCB; allopurinol: −59.2±13.1 vs. −53.5±23.3 %CVCB; tempol: −63.5±18.1 vs. −37.7±16.7 %CVCB; main effect: P &lt; 0.01). However, no interaction effect was observed for the race‐by‐site comparison (P = 0.35), suggesting no effect of the drugs used across races. In conclusion, these preliminary data suggest that BM exhibit exaggerated α1‐adrenoreceptor‐mediated vasoconstriction compared to WM, which is consistent with previous literature. Furthermore, these preliminary findings indicate this response is not superoxide‐mediated, suggestive of a different, currently unknown controlling mechanism for exaggerated vasoconstriction.Support or Funding InformationUTA Start‐up funds to R. Matthew BrothersThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Age-related attenuation of conduit artery blood flow response to passive heating differs between the arm and leg.

Little is known about why the attenuation of heat loss responses with aging begins in the lower limbs. This study sought to determine whether passive heating causes the age-related decrease and limb-specific difference of blood flow (BF) responses between conduit brachial and femoral arteries, which are related to differences of cutaneous vascular conductance (CVC) between the upper and lower limbs. In 15 older and 12 younger males, BF in the brachial and femoral arteries was ultrasonically measured and CVC in the forearm and thigh was assessed during lower leg immersion in hot water at 42°C (ambient temperature: 30°C, relative humidity: 45%) for 40min. The increased BF of brachial artery at the end of passive heating was similar between both age groups (older: 140 ± 4%; younger: 146 ± 11%), while that of femoral artery was smaller in older than younger group (119 ± 4% vs. 166 ± 11%, P < 0.01). Moreover, the increased CVC in the forearm was similar between the age groups (older: 356 ± 50%; younger: 308 ± 46%), although CVC in the thigh was significantly lower in older than younger group (303 ± 33% vs. 427 ± 51%, P < 0.05). These results corresponded to the BF responses of the brachial and femoral arteries, respectively. These results indicate that age-related decrease and limb-specific difference occur also in conduit arteries of arm and leg, which might be related to the different reduction in CVC between forearm and thigh.

Do metaboreceptors alter heat loss responses following dynamic exercise?

Metaboreceptor activation during passive heating is known to influence cutaneous vascular conductance (CVC) and sweat rate (SR). However, whether metaboreceptors modulate the suppression of heat loss following dynamic exercise remains unclear. On separate days, before and after 15 min of high-intensity treadmill running in the heat (35°C), eight males underwent either 1) no isometric handgrip exercise (IHG) or ischemia (CON), 2) 1 min IHG (60% of maximum, IHG), 3) 1 min IHG followed by 2 min of ischemia (IHG+OCC), 4) 2 min of ischemia (OCC), or 5) 1 min IHG followed by 2 min of ischemia with application of lower body negative pressure (IHG+LBNP). SR (ventilated capsule), cutaneous blood flow (Laser-Doppler), and mean arterial pressure (Finometer) were measured continuously before and after dynamic exercise. Following dynamic exercise, CVC was reduced with IHG exercise (P < 0.05) and remained attenuated with post-IHG ischemia during IHG+OCC relative to CON (39 ± 2 vs. 47 ± 6%, P < 0.05). Furthermore, the reduction in CVC was exacerbated by application of LBNP during post-IHG ischemia (35 ± 3%, P < 0.05) relative to IHG+OCC. SR increased during IHG exercise (P < 0.05) and remained elevated during post-IHG ischemia relative to CON following dynamic exercise (0.94 ± 0.15 vs. 0.53 ± 0.09 mg·min(-1)·cm(-2), P < 0.05). In contrast, application of LBNP during post-IHG ischemia had no effect on SR (0.93 ± 0.09 mg·min(-1)·cm(-2), P > 0.05) relative to post-IHG ischemia during IHG+OCC. We show that CVC is reduced and that SR is increased by metaboreceptor activation following dynamic exercise. In addition, we show that the metaboreflex-induced loading of the baroreceptors can influence the CVC response, but not the sweating response.

Elevated local skin temperature impairs cutaneous vasoconstrictor responses to a simulated haemorrhagic challenge while heat stressed

During a simulated haemorrhagic challenge, syncopal symptoms develop sooner when individuals are hyperthermic relative to normothermic. This is due, in part, to a large displacement of blood to the cutaneous circulation during hyperthermia, coupled with inadequate cutaneous vasoconstriction during the hypotensive challenge. The influence of local skin temperature on these cutaneous vasoconstrictor responses is unclear. This project tested the hypothesis that local skin temperature modulates cutaneous vasoconstriction during simulated haemorrhage in hyperthermic humans. Eight healthy participants (four men and four women; 32 ± 7 years old; 75.2 ± 10.8 kg) underwent lower-body negative pressure to presyncope while heat stressed via a water-perfused suit sufficiently to increase core temperature by 1.2 ± 0.2 °C. At forearm skin sites distal to the water-perfused suit, local skin temperature was either 35.2 ± 0.6 (mild heating) or 38.2 ± 0.2 °C (moderate heating) throughout heat stress and lower-body negative pressure, and remained at these temperatures until presyncope. The reduction in cutaneous vascular conductance during the final 90 s of lower-body negative pressure, relative to heat-stress baseline, was greatest at the mildly heated site (-10 ± 15% reduction) relative to the moderately heated site (-2 ± 12%; P = 0.05 for the magnitude of the reduction in cutaneous vascular conductance between sites), because vasoconstriction at the moderately heated site was either absent or negligible. In hyperthermic individuals, the extent of cutaneous vasoconstriction during a simulated haemorrhage can be modulated by local skin temperature. In situations where skin temperature is at least 38 °C, as is the case in soldiers operating in warm climatic conditions, a haemorrhagic insult is unlikely to be accompanied by cutaneous vasoconstriction.

Acute influence of oral vitamin C on the vasoconstrictor responses to local cooling and tyramine in human skin

It has been reported that orally ingesting vitamin C (Asc) enhanced the cutaneous vasoconstrictor response to local cooling (LC). In this study, we examined 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). Skin blood flow (SkBF) was measured by laser‐Doppler flowmetry at BT‐treated and untreated sites. The skin sites were locally cooled from 34 to 24°C at −1°C/min and maintained at 24°C for 10 min before (Pre) and 1.5 h after (Post) oral Asc (2g single dose) 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&lt;0.05) the reductions in CVC at untreated sites but did not change the responses at BT‐treated sites during LC. To further examine whether adrenergically mediated vasoconstriction is enhanced by oral Asc, 0.1mM tyramine was administered using intradermal microdialysis in the forearm skin at 34°C in the Pre and Post periods. Oral Asc increased (P&lt;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.

Local skin temperature alters cutaneous vasoconstrictor responses to a simulated hemorrhagic challenge while heat stressed

Tolerance to simulated hemorrhage is reduced with hyperthermia, due in part to inadequate cutaneous vasoconstriction. It is unclear how elevated skin temperatures, as experienced by soldiers on active duty, influence cutaneous vasoconstriction during simulated hemorrhage. 8 healthy males (34 ± 9 yr, 80.2 ± 4.2 kg) underwent a simulated hemorrhagic challenge via lower body negative pressure (LBNP) to pre‐syncope while heat stressed sufficient to increase core (Tcore Δ1.2 ± 0.2°C) and mean skin temperatures (Tsk mean 38.2 ± 0.7°C). Local skin temperatures at three forearm sites were held at 35.2±0.6°C, 38.2±0.2°C and 41.3± 0.7°C throughout heat stress and LBNP. At pre‐syncope mean arterial pressure declined (74±6 to 53 ± 8 mmHg P &lt; 0.0001) while mean Tsk (38.2±0.7°C; P = 0.92) and local Tsk (35.1±0.8; 38.3±0.3 and 41.5±0.6°C; P &gt; 0.05) were unchanged relative to heat stress baseline (i.e., pre‐LBNP). The magnitude of reduction in cutaneous vascular conductance during the final 90 seconds of LBNP from heat stress baseline was influenced by local Tsk (8% at ~35°C; 3% at ~38°C and 2% at ~42°C; P &lt; 0.0001). In hyperthermic individuals the extent of cutaneous vasoconstriction during a simulated hemorrhage is dependent on skin temperature. In situations where a soldier's skin temperature exceeds 38°C, cutaneous vasoconstriction to a hemorrhagic challenge is likely negligible.NIH HL61388 and HL84072

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

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.

Insufficient cutaneous vasoconstriction leading up to and during syncopal symptoms in the heat stressed human

As much as 50% of cardiac output can be distributed to the skin in the hyperthermic human, and therefore the control of cutaneous vascular conductance (CVC) becomes critical for the maintenance of blood pressure. Little is known regarding the magnitude of cutaneous vasoconstriction in profoundly hypotensive individuals while heat stressed. This project investigated the hypothesis that leading up to and during syncopal symptoms associated with combined heat and orthostatic stress, reductions in CVC are inadequate to prevent syncope. Using a retrospective study design, we evaluated data from subjects who experienced syncopal symptoms during lower body negative pressure (N = 41) and head-up tilt (N = 5). Subjects were instrumented for measures of internal temperature, forearm skin blood flow, arterial pressure, and heart rate. CVC was calculated as skin blood flow/mean arterial pressure × 100. Data were obtained while subjects were normothermic, immediately before an orthostatic challenge while heat stressed, and at 5-s averages for the 2 min preceding the cessation of the orthostatic challenge due to syncopal symptoms. Whole body heat stress increased internal temperature (1.25 ± 0.3°C; P < 0.001) and CVC (29 ± 20 to 160 ± 58 CVC units; P < 0.001) without altering mean arterial pressure (83 ± 7 to 82 ± 6 mmHg). Mean arterial pressure was reduced to 57 ± 9 mmHg (P < 0.001) immediately before the termination of the orthostatic challenge. At test termination, CVC decreased to 138 ± 61 CVC units (P < 0.001) relative to before the orthostatic challenge but remained approximately fourfold greater than when subjects were normothermic. This negligible reduction in CVC during pronounced hypotension likely contributes to reduced orthostatic tolerance in heat-stressed humans. Given that lower body negative pressure and head-up tilt are models of acute hemorrhage, these findings have important implications with respect to mechanisms of compromised blood pressure control in the hemorrhagic individual who is also hyperthermic (e.g., military personnel, firefighters, etc.).

Cardiovascular and Thermal Responses to Repeated Head-Up Tilts Following Exercise-Induced Heat Stress

We evaluated the acute cardiovascular and thermoregulatory responses to repeated 70 degrees head-up tilts (HUT) performed following exercise-induced hyperthermia. Eight male subjects underwent intermittent episodes of 70 degrees HUT in either a non-exercise/ non-heat stress state (NH) or an exercise-induced hyperthermic state (EIH). Subjects remained supine for 30 min in a thermoneutral environment (22 degrees C) and were subsequently exposed to three successive 6-min 70 degrees head-up tilts (HUT1, HUT2, HUT3), each separated by 10 min of supine resting. During EIH, subjects were rendered hyperthermic by exercise in the heat (core temperature of approximately 40.0 degrees C) and were then transferred to an ambient temperature of 22 degrees C. We evaluated the relative change in hemodynamic and thermal responses from the last minute in the supine position preceding the HUT to the final minute in HUT. While we measured a difference in the relative change in heart rate between conditions for all HUTs, no differences were observed in mean arterial pressure (MAP), total peripheral resistance, or cardiac output. A reduced change in baroreceptor sensitivity was measured in EIH for HUT1 only (-2 +/- 1 ms x mmHg(-1) following EIH compared to -13 +/- 3 ms x mmHg(-1) during NH). A significant transient reduction in cutaneous vascular conductance (CVC) occurred during HUT1 and HUT2 following EIH (-20 +/- 5% CVCmax and -9 +/- 3 %CVCmax, respectively), despite significant elevations in core temperature above resting levels (i.e., 1.4 degrees C and 0.9 degrees C for HUT1 and HUT2). We conclude that the maintenance of MAP following exercise in the heat is mitigated by reductions in skin perfusion despite significant elevations in core temperature.

習慣的喫煙者における長時間メンタルストレス後の喫煙は無毛部の皮膚血管をより一層収縮させる

In the present study, to test the hypothesis that cigarette smoking and physical exercise induce different influences on peripheral vasomotor control after mental stress, we examined the physiological responses, including skin vasomotor responses, to smoking and exercise in six healthy smokers. The smokers performed 2 hr of mental arithmetic tasks (MT) followed by smoking or bicycle exercise (108 +/- 7W) for 10 min or a time control (i.e., rest without smoking) under thermally comfortable conditions (25 degrees C). Skin blood flow (laser-Doppler flowmetry) was monitored at glabrous (palm) and nonglabrous (forearm, forehead) sites. Cutaneous vascular conductance (CVC) was evaluated from the ratio of blood flow to mean arterial pressure (MAP). The prolonged MT increased MAP from 77.7 +/- 2.7 mmHg to 86.0 +/- 3.0 mmHg and reduced CVC in the palm by 27.4 +/- 5.6%, but did not change those in the forearm and forehead. Smoking after MT further decreased CVC in the palm, and the smoking-induced reduction in CVC persisted until 20 min after smoking. Meanwhile, CVC in the forearm and forehead transiently and minimally decreased during smoking. Exercise after MT increased CVC at the three sites, and the exercise-induced elevation of CVC in the palm persisted until 30 min after exercise. In the time control experiments, each variable remained unchanged throughout the recovery period of MT. It was suggested that smoking causes additional vasoconstriction in glabrous skin after prolonged MT, while the exercise-associated vasodilator effect counteracts the vasoconstrictor action of MT. We speculate that long-term mental stress and smoking behavior may synergistically develop chronic stress-induced vascular dysfunction, and the stress-related disorders may be reduced by habitual enforcement of moderate exercise.

Local ascorbate administration inhibits the adrenergic vasoconstrictor response to local cooling in the human skin

Local cooling (LC) of nonglabrous skin causes vasoconstriction via the adrenergic and removal of nitric oxide (NO) systems. Since cooling increases reactive oxygen species in smooth muscle cells and induces increased sensitivity of alpha-adrenergic receptors, antioxidant supplementation may attenuate the vasoconstrictor response to skin LC via adrenergic and/or NO systems. To test this hypothesis, we examined the effects of acute L-ascorbate (Asc, 10 mM) supplementation in human skin on the vasoconstrictor responses to LC in skin with and without NO synthase (NOS) inhibition or adrenergic receptor blockade. In a three-part study, forearm sites were instrumented with microdialysis fibers, local coolers, and laser-Doppler flow (LDF) probes in healthy volunteers. Sites were cooled from 34 to 24 degrees C at -1 degrees C/min and maintained at 24 degrees C for 20 min (parts 1 and 2) or 30 min (part 3). During the last 10 min of LC in parts 1 and 2, whole body cooling was performed to increase sympathetic vasoconstrictor activity. Cutaneous vascular conductance (CVC) was calculated as the ratio of LDF to blood pressure and expressed relative to the baseline value before cooling. Treatments in each part were as follows: part 1) untreated, Asc; part 2) N(G)-nitro-L-arginine methyl ester (L-NAME) to inhibit NOS, combined L-NAME + Asc; part 3) yohimbine (YOH) + propranolol (PRO) to antagonize alpha- and beta-adrenergic receptors and combined YOH + PRO + Asc. CVC reduction during LC was smaller (P < 0.001) at Asc sites (-31 +/- 4%) than at untreated sites (-56 +/- 5%). LC-induced reduction in CVC was smaller (P < 0.05) at L-NAME + Asc sites (-23 +/- 8%) than at L-NAME sites (-43 +/- 7%). LC-induced reduction in CVC did not differ between at PRO + YOH sites (-56 +/- 3%) and at PRO + YOH + Asc sites (-50 +/- 3%). These findings suggest that antioxidant supplementation inhibits the vasoconstrictor response to direct cooling through an adrenoceptor-dependent mechanism in human skin.

Neural and non‐neural control of skin blood flow during isometric handgrip exercise in the heat stressed human

During heat stress, isometric handgrip (IHG) exercise causes cutaneous vasoconstriction, but it remains controversial whether neural mechanisms are responsible for this observation. The objective of this study was to test the hypothesis that cutaneous vasoconstriction during IHG exercise in heat stressed individuals occurs via a neural mechanism. An axillary nerve blockade was performed to block efferent nerve traffic to the left forearm in seven healthy subjects. Two intradermal microdialysis probes were placed within forearm skin of the blocked area. Forearm skin blood flow was measured by laser-Doppler flowmetry over the microdialysis probes as well as from skin of the contralateral (unblocked) forearm. Cutaneous vascular conductance (CVC) was calculated from the ratio of skin blood flow to mean arterial pressure. Effectiveness of nerve blockade was verified by the absence of tactile sensation, as well as an absence of sweating and cutaneous vasodilatation during a whole-body heat stress. Upon this confirmation, adenosine was perfused through one of the microdialysis probes to increase skin blood flow similar to that of the unblocked site. After internal temperature increased approximately 0.7 degrees C, subjects performed 2 min of IHG exercise at 35% of maximal voluntary contraction using the non-blocked arm. IHG exercise significantly decreased CVC at the unblocked site (82.3 +/- 5.7 to 70.9 +/- 5.4%max, P = 0.005, means +/- S.E.M.) and the adenosine treated site of the blocked arm (75.2 +/- 7.2 to 68.3 +/- 6.6%max, P = 0.005), whereas CVC was unchanged at the blocked site that did not receive adenosine (15.7 +/- 2.8 to 13.7 +/- 2.0%max, P = 0.10). Importantly, the reduction in CVC was greater at the unblocked site than at the adenosine treated site (11.4 +/- 2.6 vs. 6.9 +/- 1.6%max, respectively, P = 0.01). These findings suggest that neural and non-neural mechanisms contribute to the reduction in forearm CVC during IHG exercise in heat stressed humans.

Postexercise reduction in lung diffusion capacity is not attenuated by skin cooling

Pulmonary diffusion capacity for carbon monoxide (DL(CO)) is reduced by approximately 10% 1-6 h after maximal exercise. The mechanisms may be interstitial alveolar oedema and reduced pulmonary capillary blood volume. It was hypothesized that thermal stress following exercise contributes to the reduction in DL(CO), and that skin cooling would attenuate the postexercise reduction in DL(CO). Cutaneous vascular conductance (CVC), mean surface temperature (MST), rectal temperature and DL(CO) were measured before and 90 min after maximal incremental cycle exercise. Thereafter, the subjects were exposed to cold air without eliciting shivering one day and another day served as control. The measurements were repeated 120 min after exercise. Twelve healthy subjects (six male) aged 20-27 years were studied. DL(CO) was reduced by 7.1% (SD = 6.3%, P = 0.003) and 7.6% (SD = 5.3%, P<0.001) 90 and 120 min after exercise in the control experiment. It was reduced by 5.6% (SD = 5.5%, P = 0.014) 90 min after exercise and remained reduced by 6.1% (SD = 6.1%, P = 0.012) after cooling despite a significant reduction in CVC and in MST from 31.9 (SD = 0.6) degrees C to 27.4 (SD = 1.9) degrees C. We conclude that the postexercise reduction in DL(CO) is present when thermal status is restored after exercise, and that it is not influenced by further skin surface cooling.

Neural control of cutaneous vasoconstriction during lower‐body negative pressure (LBNP) in the heat stressed individual

The decrease in cutaneous vascular conductance (CVC) during LBNP in the heat stressed human could be mediated by neural and non‐neural mechanisms. This project further investigated this question. Nerve activity to a forearm was blocked (via axial blockade) in seven healthy subjects. Two intradermal microdialysis probes were placed within the skin of the blocked area. Forearm skin blood flow was measured by laser‐Doppler flowmetry over these microdialysis probes, as well as from skin of the contralateral (non‐blocked) forearm. The absence of sweating and cutaneous vasodilation during heat stress confirmed an effective block. Upon this confirmation, adenosine was perfused through one microdialysis probe to increase skin blood flow similar to that of the non‐blocked site. After internal temperature was elevated ~1.0 °C, 30 mmHg LBNP was applied for 10 min, or until the onset of presyncopal symptoms. LBNP significantly decreased CVC at all three sites (unblocked site: −6.1±2.7; blocked site: −2.5±1.3%max; blocked site with adenosine: −5.4±2.2%max), although the magnitude of reduction in CVC was not different between unblocked and adenosine sites. When combined with prior data, these findings suggest that reductions in CVC to LBNP of heat stressed individuals could have both neural and non‐neural components.Study funded by part by NIH HL61388 &amp; HL84072

Endogenous nitric oxide attenuates neutrally mediated cutaneous vasoconstriction

Cutaneous vasoconstrictor responsiveness may be impaired by substance(s) directly or indirectly responsible for cutaneous active vasodilatation. In this study, we tested the hypothesis that endogenous nitric oxide (NO) attenuates the reduction in cutaneous vascular conductance (CVC) during an orthostatic challenge combined with whole-body heating, as well as during whole-body cooling. In protocol 1, healthy subjects were pretreated with an intradermal injection of botulinum toxin A (BTX) to block the release of neurotransmitters from nerves responsible for cutaneous active vasodilatation. On the experimental day, a microdialysis probe was placed at the BTX-treated site as well as at two adjacent untreated sites. NG-nitro-l-arginine methyl ester (L-NAME, 10 mm) was perfused through the probe placed at the BTX-treated site and at one untreated site. After confirmation of the absence of cutaneous vasodilatation at the BTX site during whole-body heating, adenosine was infused through the microdialysis probe at this site to increase skin blood flow to a level similar to that at the untreated site. Subsequently, 30 and 40 mmHg lower-body negative pressures (LBNPs) were applied. The reduction in CVC to LBNP was greatest at the BTX-treated site (15.0 +/- 2.4% of the maximum level (% max)), followed by the L-NAME-treated site (11.3 +/- 2.6% max), and then the untreated site (3.8 +/- 3.0% max; P < 0.05 for all comparisons). In protocol 2, two microdialysis membranes were inserted in the dermal space of one forearm. Adenosine alone was infused at one site while the other site received adenosine and L-NAME. The reduction in CVC in response to whole-body cooling was significantly greater at the L-NAME-treated site than at the adjacent adenosine alone site. These results suggest that endogenous NO is capable of attenuating cutaneous vasoconstrictor responsiveness.

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

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 degrees 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.

Does local heating-induced nitric oxide production attenuate vasoconstrictor responsiveness to lower body negative pressure in human skin?

We tested the hypothesis that local heating-induced nitric oxide (NO) production attenuates cutaneous vasoconstrictor responsiveness. Eleven subjects (6 men, 5 women) had four microdialysis membranes placed in forearm skin. Two membranes were perfused with 10 mM of N(G)-nitro-L-arginine (L-NAME) and two with Ringer solution (control), and all sites were locally heated to 34 degrees C. Subjects then underwent 5 min of 60-mmHg lower body negative pressure (LBNP). Two sites (a control and an L-NAME site) were then heated to 39 degrees C, while the other two sites were heated to 42 degrees C. At the L-NAME sites, skin blood flow was elevated using 0.75-2 mg/ml of adenosine in the perfusate solution (Adn + L-NAME) to a similar level relative to control sites. Subjects then underwent another 5 min of 60-mmHg LBNP. At 34 degrees C, cutaneous vascular conductance (CVC) decreased (Delta) similarly at both control and L-NAME sites during LBNP (Delta7.9 +/- 3.0 and Delta3.4 +/- 0.8% maximum, respectively; P > 0.05). The reduction in CVC to LBNP was also similar between control and Adn + L-NAME sites at 39 degrees C (control Delta11.4 +/- 2.5 vs. Adn + L-NAME Delta7.9 +/- 2.0% maximum; P > 0.05) and 42 degrees C (control Delta1.9 +/- 2.7 vs. Adn + L-NAME Delta 4.2 +/- 2.7% maximum; P > 0.05). However, the decrease in CVC at 42 degrees C, regardless of site, was smaller than at 39 degrees C (P < 0.05). These results do not support the hypothesis that local heating-induced NO production attenuates cutaneous vasoconstrictor responsiveness during high levels of LBNP. However, elevated local temperature, per se, attenuates cutaneous vasoconstrictor responsiveness to LBNP, presumably through non-nitric oxide mechanisms.

Endogenous NO decreases cutaneous vasoconstrictor responsiveness during lower‐body negative pressure (LBNP) in the heat stressed individual

Previously we reported that, in the heat stressed human, substance(s) presumably released from the cutaneous vasodilator system attenuate the effectiveness of the cutaneous vasoconstrictor system during orthostatic stress. This study tested the hypothesis that endogenous nitric oxide (NO) contributes to the attenuation of the reduction in cutaneous vascular conductance (CVC) during these combined stresses. Two microdialysis probes were placed in dorsal forearm skin of seven healthy volunteers. Skin blood flow was monitored over each microdialysis membrane. CVC was calculated from the ratio of skin blood flow to mean arterial pressure. One membrane was perfused with the NO synthase inhibitor, L-NAME, while the adjacent membrane served as an untreated control site. After internal temperature was elevated ~0.7°C via whole-body heating, 30 mmHg LBNP was applied for 3 min immediately followed by 3 min of 40 mmHg LBNP, or until the onset of presyncopal symptoms. The reduction in CVC during LBNP was significantly greater at the L-NAME treated site relative to the control site (−10.4±7.3 vs. −2.0±7.2%max, P<0.05), despite CVC prior to LBNP being lower at the L-NAME site (48.7±5.2 vs. 58.6±5.9%max, P<0.05). These data suggest that endogenous NO is capable of attenuating the reduction in CVC during an orthostatic challenge of heat stressed humans. Study funded by part by NIH HL61388, HL67422, & HL84072