Cutaneous Vascular Conductance Responses Research Articles

Dietary NO3− does not enhance endothelial dependent cutaneous vascular conductance in older women

Prior work has yet to determine whether the reduction of dietary nitrate (NO3−) to NO, via the enterosalivary pathway, may modify cutaneous vascular conductance (CVC) responses to local heating in older women. Changes occurring with the transition to menopause related to hormonal flux, increased adiposity, and/or decreased physical activity may further compound the negative influence of aging on nitric oxide (NO)-dependent CVC. Herein, we characterized changes in NO-dependent CVC following acute ingestion of 140 mL of NO3−-rich beetroot juice in 24 older women (age: 65 ± 5 y, BMI: 31.2 ± 3.7 kg/m2). Red blood cell (RBC) flux was measured continuously via laser-Doppler flowmetry on the dorsal aspect of the forearm during local skin heating to 39 °C/44 °C before and 3 h after NO3− ingestion. NO-dependent changes in CVC were calculated as RBC flux/mean arterial blood pressure at 39 °C and normalized as a proportion of maximal CVC at 44 °C (%CVCmax). Changes (Δ) in fractional exhaled NO (FeNO) following NO3− ingestion were used an index of NO bioavailability. Despite increased FeNO (+81 ± 70 %, P < 0.001), %CVCmax at 39 °C was reduced (−16 ± 10 %, P < 0.001) following NO3− ingestion. A greater reduction in %CVCmax was weakly to moderately associated with higher body fat% (r = 0.45 [0.05–0.72], P = 0.029), central adiposity% (r = 0.50 [0.13–0.75], P = 0.012), neutrophil% (r = 0.42 [0.02–0.70], P = 0.041), and higher neutrophil to lymphocyte ratio (r = 0.49 [0.11–0.75], P = 0.016). These findings demonstrate a single dose of dietary NO3− does not promote CVC responses to local heating in sedentary older women with overweight and obesity. Correlation with multiple biomarkers suggest systemic inflammation may be involved.

Cutaneous microvascular vasodilatory consequences of acute consumption of a caffeinated soft drink sweetened with high-fructose corn syrup.

This study tested the hypotheses that compared to drinking water, consumption of a caffeinated soft drink sweetened with high‐fructose corn syrup (HFCS) attenuates the cutaneous vasodilatory response to local skin heating without (Protocol 1) and following ischemia‐reperfusion injury (Protocol 2). In a randomized, counterbalanced crossover design, 14 healthy adults (25 ± 3 year, 6 women) consumed 500 ml of water (water) or a caffeinated soft drink sweetened with HFCS (Mtn. Dew, DEW). Thirty minutes following beverage consumption local skin heating commenced on the right forearm (Protocol 1), while on the left forearm ischemia‐reperfusion commenced with 20 min of ischemia followed by 20 min of reperfusion and then local skin heating (Protocol 2). Local skin heating involved 40 min of heating to 39℃ followed by 20 min of heating to 44℃. Skin blood flow (SkBf, laser Doppler) data were normalized to mean arterial pressure and are presented as a cutaneous vascular conductance (CVC) and as percentage of the CVC response during heating to 44℃ (%CVCmax). Protocol 1: During local heating at 39℃, no differences were observed in CVC (water: 2.0 ± 0.6 PU/mmHg; DEW: 2.0 ± 0.8 PU/mmHg, p = 0.83) or %CVCmax (water: 59 ± 14%; DEW 60 ± 15%, p = 0.84) between trials. Protocol 2: During local skin heating at 39℃, no differences were observed in CVC (water: 1.7 ± 0.5 PU/mmHg; DEW: 1.5 ± 0.5 PU/mmHg, p = 0.33) or %CVCmax (water: 64 ± 15%; DEW 61 ± 15% p = 0.62) between trials. The cutaneous microvascular vasodilator response to local heating with or without prior ischemia‐reperfusion injury is not affected by acute consumption of a caffeinated soft drink sweetened with HFCS.

ACUTE DIETARY NITRATE MAY IMPAIR CUTANEOUS VASCULAR CONDUCTANCE DURING LOCAL SKIN HEATING IN POSTMENOPAUSAL WOMEN

Declining estradiol production during menopause is linked to increased oxidative stress and reduced endothelial-dependent vasodilation. It is unknown whether supplementation with dietary nitrate may improve nitric oxide (NO) bioactivity and microvascular function in postmenopausal women. PURPOSE: To determine the effects of acute dietary nitrate ingestion on NO-mediated cutaneous vascular conductance (CVC) in a cohort of postmenopausal women. METHODS: In eight women (mean ± SD: age = 62 ± 4 y, BMI = 31 ± 2 kg/m2), two laser-Doppler flowmetry probes were affixed to the dorsal aspect of the forearm for measurement of red blood cell (RBC) flux during local skin heating to 39 °C and 44 °C. Assessments were made before and 3 h after ingesting 140 mL of beetroot juice containing 12.9 mmoL of inorganic nitrate. Fractional exhaled nitric oxide (FeNO) concentrations were measured at the same time points. Cutaneous vascular conductance (CVC) at 39 °C was calculated as RBC flux/ mean arterial pressure then normalized as a proportion of maximal CVC at 44°C. During the plateau phase at 39 °C, median spectral power of the endothelial NO-dependent frequency interval was analyzed using a Morlet wavelet transform. Pre-post comparisons were performed using within-sample t-tests. RESULTS: Following beetroot juice ingestion, FeNO concentrations (mean ± SD: 18 ± 8 ppb vs. 35 ± 16 ppb; p = 0.006, dz = 1.4) and spectral power of the NO-dependent frequency interval (0.01 - 0.02 Hz; p = 0.018, dz = 1.1) increased. Despite evidence for greater NO bioavailability, CVC at 39 °C was reduced (76 ± 12% vs. 50 ± 18%; p < 0.001, dz = 2.3). There was no change in maximal CVC at 44 °C (p = 0.287). CONCLUSION: A functional consequence of increased NO-bioavailability with acute dietary nitrate ingestion appears to be a diminished NO-mediated CVC response to local skin heating in our cohort of postmenopausal women with overweight and obesity. Future research should consider the effects of dietary nitrate coupled with an antioxidant supplement as means to further support NO-mediated endothelial function in such populations.

Endothelium‐Independent, but Not Endothelium‐Dependent, Human Microvascular Vasodilation Differs Between Young, Healthy Females and Males

Estrogen increases nitric oxide production, but a direct comparison of endothelium-dependent and endothelium-independent mechanisms of human microvascular vasodilation between females and males has not been completed. The purpose of this study was to examine endothelium-dependent and endothelium-independent mechanisms of human cutaneous microvascular vasodilation between young, healthy females and males. Females were grouped by menstrual cycle phase to assess the influence of female sex hormones. We hypothesized that females in menstrual cycle phases of elevated estrogen would have an increased endothelium-dependent vasodilation response compared to females in phases of decreased estrogen or males. Eighteen participants (7 males; 6 females in early follicular phase, F-EF; 5 females in luteal phase, F-L) were instrumented with two microdialysis fibers in the skin of the forearm. A dose-response was completed at each site: 1) acetylcholine (ACh; 10-10 – 10-1 M) to assess endothelium-dependent vasodilation, and 2) sodium nitroprusside (SNP; 10-10 – 10-1 M) to assess endothelium-independent vasodilation. Doses were perfused for 5 minutes. Maximal vasodilation was elicited by heating the skin to 43°C and infusing 54 mM SNP. Laser-Doppler flowmetry (LDF) provided an index of skin blood flow. Cutaneous vascular conductance (CVC) was calculated (LDF/mean arterial pressure) and normalized to maximal blood flow (%CVCmax). Data are presented as mean ± SD. There was no interaction between main effects of group and dose in %CVCmax response to ACh, but there was a main effect of dose (p < 0.0001). The ACh logEC50 was similar between all groups (males: -3.8 ± 0.76M; F-EF: -2.7 ± 1.00M; F-L: -4.0 ± 0.61M). There was a significant interaction between group and dose in %CVCmax response to SNP (p = 0.04). At 10-4 M SNP, F-L (20 ± 9%CVCmax) displayed a lower response compared to males (46 ± 19%CVCmax, p = 0.004). At 10-3 M SNP, F-EF (46 ± 25%CVCmax, p = 0.038) and F-L (36 ± 15%CVCmax, p = 0.002) displayed lower responses compared to males (64 ± 16%CVCmax). The response to 10-2 M and 10-1 M SNP were not statistically different between groups. The SNP logEC50 was not different between F-EF and F-L; however, the SNP logEC50 was lower in males (-4.6 ± 0.47M) compared to F-EF (-3.3 ± 0.64M, p = 0.02) and F-L (-2.8 ± 0.36M, p < 0.0001). There was no difference between groups or phase for maximal CVC responses (p > 0.05). Endothelium-dependent mechanisms of microvascular vasodilation were similar between males and females, regardless of menstrual cycle phase. Males displayed heightened endothelium-independent vasodilation in response to lower doses of SNP, but also appeared to exhibit tachyphylaxis at the higher concentrations, compared to females.

Exercise training improves microvascular function in patients with Chagas heart disease: Data from the PEACH study

BackgroundChagas heart disease (CHD) impairs the systemic microvascular function. We investigated the effects of exercise training on cutaneous microvascular function among patients with CHD. MethodsPatients from the PEACH study were randomly assigned to a supervised exercise training 3 times/week for 6 months (Trained; n = 10) or a control group (Untrained; n = 8). Both groups underwent evaluation of microvascular function before, and at 3- and 6-months of follow-up. Cutaneous vascular conductance (CVC) was assessed in the skin of the forearm using laser speckle contrast imaging coupled with iontophoresis of acetylcholine (ACh), sodium nitroprusside (SNP) and during post-occlusive reactive hyperemia (PORH). ResultsAt 3-months of follow-up, no difference was detected between groups in CVC responses to ACh (p = 0.50), SNP (p = 0.26) and HRPO (p = 0.65). However, at 6-months of follow-up, trained vs. untrained patients improved CVC induced by SNP-iontophoresis (0.19 ± 0.10 vs. 0.14 ± 0.15 APU.mmHg−1; p = 0.05) and PORH (0.63 ± 0.15 vs. 0.48 ± 0.18 APU.mmHg−1; p = 0.05). CVC response to ACh-iontophoresis was similar between groups (0.19 ± 0.11 vs. 0.22 ± 0.17 APU.mmHg−1; p = 0.38). ConclusionExercise training performed during 6 months improved the cutaneous microvascular function of CHD patients. Further studies evaluating the mechanism involved in this response are warranted.

Regional influence of nitric oxide on cutaneous vasodilatation and sweating during exercise‐heat stress in young men

What is the central question of this study? Do regional differences exist in nitric oxide synthase (NOS)-dependent cutaneous vasodilatation and sweating during exercise-heat stress in young men. What is the main finding and its importance? Exercise-induced increases in cutaneous vasodilatation and sweating were greater on the chest and upper back compared to the forearm, although the NOS contribution to cutaneous vasodilatation was similar across all regions. Conversely, there was a greater NOS-dependent rate of change in sweating on the chest compared to the forearm, with a similar trend on the back. While it is established that nitric oxide synthase (NOS) is an important modulator of forearm cutaneous vasodilatation and sweating during an exercise-heat stress in young men, it remains unclear if regional differences exist in this response. In 15 habitually active young men (24±4 (SD) years), cutaneous vascular conductance (CVC) and local sweat rate (LSR) were assessed at three body regions. On each of the dorsal forearm, chest and upper-back (trapezius), sites were continuously perfused with either (1) lactated Ringer solution (control) or (2) 10Mm Nω -nitro-l-arginine (l-NNA, NOS inhibitor), via microdialysis. Participants rested in the heat (35°C) for ∼75min, followed by 60min of semi-recumbent cycling performed at a fixed rate of heat production of 200 Wm-2 (equivalent to ∼42% ). During exercise, the chest and upper-back regions showed higher CVC and LSR responses relative to the forearm (all P<0.05). Within each region, l-NNA attenuated CVC and LSR relative to control (all P<0.05). However, the NOS contribution was not different across regions for the rate of change and plateau for CVC or for the LSR plateau (all P>0.05). Conversely, there was a greater NOS contribution to the rate of change for LSR at the chest relative to the forearm (P<0.05) with a similar trend for the back. In habitually active young men, NOS-dependent cutaneous vasodilatation was similar across regions while the NOS contribution to LSR was greater on the chest relative to the forearm. These findings advance our understanding of the mechanisms influencing regional variations in cutaneous vasodilatation and sweating during an exercise-heat stress.

Microvascular Vasodilatory Consequences of Acute Consumption of a High Fructose Caffeinated Soft Drink

PurposeExcessive intake of high fructose sugar sweetened beverages is associated with a greater risk of cardiovascular disease. This increased risk may be attributed, in part, to fructose‐mediated elevations in vasoconstrictor tone. Compared to water, consumption of a high fructose caffeinated soft drink elicits vasoconstriction in the kidneys and augments the renal vasoconstrictor response during sympathetic stimulation. It is unknown if these observed effects are specific to the kidneys or are indicative of a systemic vascular response. Endothelial dysfunction, which is characterized by a pro‐vasoconstrictor shift mostly due to reductions in nitric oxide bioavailability, is one of the earliest pathogenic vascular changes leading to cardiovascular disease. Experimental investigation of microvascular endothelial function may offer insight into the mechanisms contributing to the elevated cardiovascular disease risk associated with intake of high fructose sugar sweetened beverages. Therefore, the purpose of this study was to test the hypothesis that acute consumption of a high fructose caffeinated soft drink attenuates the cutaneous microvascular vasodilatory response to local heating, a primarily nitric oxide mediated response.MethodsIn a randomized cross‐over design, 8 healthy adults (26 ± 2 y, 4 women) consumed either 500 mL of a high‐fructose caffeinated beverage (Mountain Dew®, Soda) or 500 mL of water (H2O) while resting supine. Red blood cell flux, an index of skin blood flow, was measured at two sites on the dorsal aspect of the forearm using laser‐Doppler flowmetry probes seated in a local heater. Skin blood flow, blood pressure (finger photoplethysmography) and heart rate (ECG) were continuously measured. Data were analyzed at baseline, 30 min post‐consumption, and the last 5 min following 40 min of local heating at 39°C and 20 min of local heating at 44°C. Heating at 39°C was chosen because at this skin temperature and duration of heating the skin blood flow response is primarily nitric oxide dependent. Skin blood flow measures were averaged between sites and expressed as cutaneous vascular conductance (CVC), calculated as skin blood flow divided by mean arterial pressure. Data are presented as a percentage of the CVC response to local heating at 44°C (CVCmax).ResultsMean arterial pressure did not differ between Soda and H2O at any time‐point (P=0.82). Heart rate was higher in Soda during local heating to 44°C (56 ± 7 vs. 52 ± 8 bpm, P=0.04), but did not differ at any other time‐point (P≥0.35). CVCmax did not differ between the Soda (3.5 ± 1.2 PU/mmHg) and H2O (3.4 ± 0.5 PU/mmHg) trials (P=0.82). CVC 30 min post‐consumption (Soda: 9 ± 7, H2O: 13 ± 18% CVCmax, P=0.53) or during local heating at 39°C (Soda: 58 ± 17, H2O: 58 ± 18% CVCmax, P=0.91) were not different between Soda and H2O.ConclusionsThese preliminary findings suggest the cutaneous microvascular vasodilator response to local heating is not affected by acute consumption of high fructose caffeinated beverage. It is possible that the vasoconstrictor response following acute high fructose caffeinated soft drink consumption may be specific to the kidneys and that systemic changes may not occur.

Effects of supervised exercise training on lower-limb cutaneous microvascular reactivity in adults with venous ulcers

PurposeTo investigate the effects of a 12-week supervised exercise programme on lower-limb cutaneous microvascular reactivity in adults with venous leg ulceration.MethodsThirty-eight adults with unilateral venous ulceration who were being treated with lower-limb compression therapy (58% male; mean age 65 years; median ulcer size 5 cm2) were randomly allocated to exercise or control groups. Exercise participants (n = 18) were invited to attend thrice weekly sessions of lower-limb aerobic and resistance exercise for 12 weeks. Cutaneous microvascular reactivity was assessed in the gaiter region of ulcerated and non-ulcerated legs at baseline and 3 months using laser Doppler fluxmetry coupled with iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). Cutaneous vascular conductance (CVC) was calculated as laser Doppler flux (AU)/mean arterial pressure (mmHg).ResultsThirty-seven participants completed follow-up assessments. Median session attendance was 36 (range 2–36). Analyses of covariance revealed greater peak CVC responses to ACh in the exercise group at 3 months in both the ulcerated (adjusted difference = 0.944 AU/mmHg; 95% CI 0.504–1.384) and non-ulcerated (adjusted difference = 0.596 AU/mmHg; 95% CI 0.028–1.164) legs. Peak CVC responses to SNP were also greater in the exercise group at 3 months in the ulcerated leg (adjusted difference = 0.882 AU/mmHg; 95% CI 0.274–1.491), but not the non-ulcerated leg (adjusted difference = 0.392 AU/mmHg; 95% CI − 0.377 to 1.161).ConclusionSupervised exercise training improves lower-limb cutaneous microvascular reactivity in adults with venous leg ulceration.

Ten days of repeated local forearm heating does not affect cutaneous vascular function.

The aim of the present study was to determine whether 10 days of repeated local heating could induce peripheral adaptations in the cutaneous vasculature and to investigate potential mechanisms of adaptation. We also assessed maximal forearm blood flow to determine whether repeated local heating affects maximal dilator capacity. Before and after 10 days of heat training consisting of 1-h exposures of the forearm to 42°C water or 32°C water (control) in the contralateral arm (randomized and counterbalanced), we assessed hyperemia to rapid local heating of the skin (n = 14 recreationally active young subjects). In addition, sequential doses of acetylcholine (ACh, 1 and 10 mM) were infused in a subset of subjects (n = 7) via microdialysis to study potential nonthermal microvascular adaptations following 10 days of repeated forearm heat training. Skin blood flow was assessed using laser-Doppler flowmetry, and cutaneous vascular conductance (CVC) was calculated as laser-Doppler red blood cell flux divided by mean arterial pressure. Maximal cutaneous vasodilation was achieved by heating the arm in a water-spray device for 45 min and assessed using venous occlusion plethysmography. Forearm vascular conductance (FVC) was calculated as forearm blood flow divided by mean arterial pressure. Repeated forearm heating did not increase plateau percent maximal CVC (CVCmax) responses to local heating (89 ± 3 vs. 89 ± 2% CVCmax, P = 0.19), 1 mM ACh (43 ± 9 vs. 53 ± 7% CVCmax, P = 0.76), or 10 mM ACh (61 ± 9 vs. 85 ± 7% CVCmax, P = 0.37, by 2-way repeated-measures ANOVA). There was a main effect of time at 10 mM ACh (P = 0.03). Maximal FVC remained unchanged (0.12 ± 0.02 vs. 0.14 ± 0.02 FVC, P = 0.30). No differences were observed in the control arm. Ten days of repeated forearm heating in recreationally active young adults did not improve the microvascular responsiveness to ACh or local heating.NEW & NOTEWORTHY We show for the first time that 10 days of repeated forearm heating is not sufficient to improve cutaneous vascular responsiveness in recreationally active young adults. In addition, this is the first study to investigate cutaneous cholinergic sensitivity and forearm blood flow following repeated local heat exposure. Our data add to the limited studies regarding repeated local heating of the cutaneous vasculature.

Investigating the roles of core and local temperature on forearm skin blood flow

We sought to isolate the contributions of core and local temperature on forearm skin blood flow (SkBF), and to examine the interaction between local- and reflexive-mechanisms of SkBF control. Forearm SkBF was assessed using laser-Doppler flowmetry in eight males and eight females during normothermia and hyperthermia (+1.2°C rectal temperature). Mean experimental forearm temperature was manipulated in four, 5min blocks between neutral (A: 33.0°C) and warm (B: 38.5°C) in an A–B–A–B fashion during normothermia, and B–A–B–A during hyperthermia. Mean control forearm skin temperature was maintained at ~33°C. Finally, local heating to 44°C was performed on both forearms to elicit maximal SkBF. Data are presented as a percentage of maximal cutaneous vascular conductance (CVC), calculated as laser-Doppler flux divided by mean arterial pressure. No sex differences were observed in any CVC measures (P>0.05). During normothermia, increasing experimental forearm temperature to 38.5°C elevated CVC by 42±8%max (d=3.1, P<0.001). Subsequently decreasing experimental forearm temperature back down to 33.0°C reduced CVC by 36±7%max (d=2.5, P<0.001). Finally, the second increase in experimental forearm temperature to 38.5°C increased CVC by 25±6%max (d=1.9, P<0.0001). During hyperthermia, decreasing experimental forearm temperature to 33.0°C reduced CVC by 6±1%max (d=0.5, P<0.001). Increasing experimental forearm temperature to 38.5°C increased CVC by 4±2%max (d=0.4, P<0.001). Finally, decreasing experimental forearm temperature to 33.0°C reduced CVC by 8±2%max (d=0.7, P<0.001). Compared to normothermia, CVC responses to local temperature changes during hyperthermia were almost abolished (normothermia: d=1.9–3.1; hyperthermia: d=0.4–0.7). These data indicate that local temperature drives SkBF during normothermia, while reflexive mechanisms regulate SkBF during hyperthermia.

Seven-Day Remote Ischemic Preconditioning Improves Local and Systemic Endothelial Function and Microcirculation in Healthy Humans

Ischemic preconditioning (IPC) protects tissue against ischemia-induced injury inside and outside ischemic areas. The purpose was to examine the hypothesis that daily IPC leads to improvement in endothelial function and skin microcirculation not only in the arm exposed to IPC but also in the contralateral arm. Thirteen healthy, young, normotensive male individuals (aged 22±2 years) were assigned to 7-day daily exposure of the arm to IPC (4×5 minutes). Assessment of brachial artery endothelial function (using flow-mediated dilation (FMD)) and forearm microcirculation (cutaneous vascular conductance (CVC) at baseline and during local heating) was performed before and after 7 days to examine the local (i.e., intervention arm) and remote (i.e., control arm) effect of IPC. We repeated the assessment tests 8 days after the intervention (Post+8). FMD increased after repeated IPC (P = 0.03) and remained significantly elevated at Post+8 in the intervention (5.0±2.2%, 6.1±2.2%, and 6.6±2.3%) and contralateral arms (5.4±2.2%, 6.0±2.2%, and 7.5±2.2%). Forearm CVC also increased following repeated IPC (P = 0.006) and remained elevated at Post+8 in both arms (intervention: 0.12±0.03, 0.14±0.04, 0.16±0.04 mV/mm Hg; contralateral: 0.14±0.04, 0.015±0.04, 0.17±0.07). No interaction between IPC arm and time was evident for FMD and CVC (both P > 0.05). IPC intervention did not alter CVC responses to local heating (P > 0.05). Daily exposure to IPC for 7 days leads to local and remote improvements in brachial artery FMD and resting skin microcirculation that remain after cessation of the intervention and beyond the late phase of protection. These findings may have clinical relevance for micro- and macrovascular improvements.

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.

Effect of decompression-induced bubble formation on highly trained divers microvascular function

We previously showed microvascular alteration of both endothelium-dependent and -independent reactivity after a single SCUBA dive. We aimed to study mechanisms involved in this postdive vascular dysfunction. Ten divers each completed three protocols: (1) a SCUBA dive at 400 kPa for 30 min; (2) a 41-min duration of seawater surface head immersed finning exercise to determine the effect of immersion and moderate physical activity; and (3) a simulated 41-min dive breathing 100% oxygen (hyperbaric oxygen [HBO]) at 170 kPa in order to analyze the effect of diving-induced hyperoxia. Bubble grades were monitored with Doppler. Cutaneous microvascular function was assessed by laser Doppler. Endothelium-dependent (acetylcholine, ACh) and -independent (sodium nitroprusside, SNP) reactivity was tested by iontophoresis. Endothelial cell activation was quantified by plasma Von Willebrand factor and nitric oxide (NO). Inactivation of NO by oxidative stress was assessed by plasma nitrotyrosine. Platelet factor 4 (PF4) was assessed in order to determine platelet aggregation. Blood was also analyzed for measurement of platelet count. Cutaneous vascular conductance (CVC) response to ACh delivery was not significantly decreased by the SCUBA protocol (23 ± 9% before vs. 17 ± 7% after; P = 0.122), whereas CVC response to SNP stimulation decreased significantly (23 ± 6% before vs. 10 ± 1% after; P = 0.039). The HBO and immersion protocols did not affect either endothelial-dependent or -independent function. The immersion protocol induced a significant increase in NO (0.07 ± 0.01 vs. 0.12 ± 0.02 μg/mL; P = 0.035). This study highlighted change in microvascular endothelial-independent but not -dependent function in highly trained divers after a single air dive. The results suggest that the effects of decompression on microvascular function may be modified by diving acclimatization.

Effects of Nitric Oxide Synthase Inhibition on Cutaneous Vasodilation in Response to Acupuncture Stimulation in Humans

The aim of the present study was to elucidate the mechanism of cutaneous vasodilation following acupuncture stimulation by investigating the roles of nitric oxide (NO) and axon reflex vasodilation. The subjects were 17 healthy male volunteers. The role of NO was investigated by administering N(G)-nitro-l-arginine methyl ester hydrochloride (L-NAME, 20 mM), an NO synthase inhibitor or Ringer's solution (control site), via intradermal microdialysis (protocol 1; n=7). The role of axon reflex vasodilation by local sensory neurones was investigated by comparing vasodilation at sites treated with 'eutectic mixture of local anaesthetics' (EMLA) cream (2.5% lidocaine and 2.5% prilocaine) with untreated sites (control site) (protocol 2; n=10). After 5 min of baseline recording, acupuncture was applied to PC4 and a control site in proximity to PC4 for 10 min and scanning was performed for 60 min after acupuncture stimulation. Skin blood flow (SkBF) was evaluated by laser Doppler perfusion imaging. Cutaneous vascular conductance (CVC) was calculated from the ratio of SkBF to mean arterial blood pressure. In the first protocol, sites administered L-NAME showed significant reductions in CVC responses following acupuncture stimulation compared to control sites (administered Ringer's solution) (p<0.05). In the second protocol, changes in CVC responses after acupuncture stimulation did not differ significantly between treated sites with EMLA cream and untreated sites (p>0.05). These data suggest that cutaneous vasodilation in response to acupuncture stimulation may not occur through an axon reflex as previously reported. Rather, NO mechanisms appear to contribute to the vasodilator response.

Nitric oxide and receptors for VIP and PACAP in cutaneous active vasodilation during heat stress in humans

VPAC2 receptors sensitive to vasoactive intestinal polypeptide (VIP) and pituitary adenylyl cyclase activating polypeptide (PACAP), PAC1 receptors sensitive to PACAP, and nitric oxide (NO) generation by NO synthase (NOS) are all implicated in cutaneous active vasodilation (AVD) through incompletely defined mechanisms. We hypothesized that VPAC2/PAC1 receptor activation and NO are synergistic and interdependent in AVD and tested our hypothesis by examining the effects of VPAC2/PAC1 receptor blockade with and without NOS inhibition during heat stress. The VPAC2/PAC1 antagonist, pituitary adenylate cyclase activating peptide 6-38 (PACAP6-38) and the NOS inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME) were administered by intradermal microdialysis. PACAP6-38, l-NAME, a combination of PACAP6-38 and l-NAME, or Ringer's solution alone were perfused at four separate sites. Skin blood flow was monitored by laser-Doppler flowmetry at each site. Body temperature was controlled with water-perfused suits. Blood pressure was monitored by Finapres, and cutaneous vascular conductance (CVC) calculated (CVC = laser-Doppler flowmetry/mean arterial pressure). The protocol began with a 5- to 10-min baseline period without antagonist perfusion, followed by perfusion of PACAP6-38, l-NAME, or combined PACAP6-38 and l-NAME at the different sites in normothermia (45 min), followed by 3 min of whole body cooling. Whole body heating was then performed to induce heat stress and activate AVD. Finally, 58 mM sodium nitroprusside were perfused at all sites to effect maximal vasodilation for normalization of blood flow data. No significant differences in CVC (normalized to maximum) were found among Ringer's PACAP6-38, l-NAME, or combined antagonist sites during normothermia (P > 0.05 among sites) or cold stress (P > 0.05 among sites). CVC responses at all treated sites were attenuated during AVD (P < 0.05 vs. Ringer's). Attenuation was greater at l-NAME and combined PACAP6-38- and l-NAME-treated sites than at PACAP6-38 sites (P > 0.05). Because responses did not differ between l-NAME and combined treatment sites (P > 0.05), we conclude that VPAC2/PAC1 receptors require NO in series to effect AVD.

Endurance exercise training enhances cutaneous microvascular reactivity in post-menopausal women

ObjectiveTo compare cutaneous microvascular reactivity between untrained young and post-menopausal women, and assess the effects of 48weeks of endurance exercise training on cutaneous microvascular reactivity in post-menopausal women. MethodsTwenty post-menopausal and 12 young women completed this study. Using laser-Doppler flowmetry, an index of skin blood flow was measured on the forearm at rest, during post-occlusive reactive hyperaemia (PORH), and during localised heating to 42°C. Cutaneous vascular conductance (CVC) was calculated as the ratio of laser-Doppler flow to mean arterial pressure (in AUmmHg−1). For the post-menopausal women, this assessment was also performed after 6, 12, 24, 36, and 48weeks of endurance exercise training. ResultsPORH and maximum CVC responses were depressed in untrained post-menopausal women compared with young controls (P≤0.011 for all methods of data expression). PORH was increased (P<0.05) in the post-menopausal women after 24weeks of exercise training (0.51±0.16 vs. 0.65±0.23AUmmHg−1), with further increases after 36 and 48weeks (0.76±0.27 and 0.88±0.32AUmmHg−1, respectively). Similarly, maximum CVC was increased (P<0.05) after 24weeks (2.20±0.31 vs. 2.66±0.27AUmmHg−1), and at the 36-week assessment (2.90±0.30AUmmHg−1). Cardiopulmonary fitness (V˙O2max) increased after 12weeks (23.5±4.4 vs. 25.4±5.1mLkg−1min−1; P<0.05), and improved further throughout the intervention (31.6±5.9mLkg−1min−1 at week 48). There was a moderate positive relationship between the change in PORH (in AUmmHg−1) between weeks 0 and 48 and the concomitant change in V˙O2max (r=0.65, P=0.002). After 24–36weeks of exercise training, the PORH and maximum CVC responses of the post-menopausal women did not differ to those of the young untrained women (P>0.05). ConclusionCutaneous microvascular reactivity is reduced in post-menopausal women compared to young controls and increased to similar levels after 24–36weeks of mild-to-moderate endurance exercise.

Assessment of Vascular Function in HIV-Infected Patients

Purpose: The vascular function in HIV-infected persons under HAART and non-HIV-infected persons was investigated.Method: 18 HIV-positive patients and 23 HIV-negative subjects (14 younger group and 9 older group) were evaluated for microvascular vasodilatation during postocclusive reactive hyperemia (PORH) and during prolonged local thermal hyperemia; overall microvascular flux increase induced by iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP_DVP); Cutaneous vascular conductance (CVC) responses to ACh were lower in HIV patients compared to both HIV-negative groups (mean [SEM]) (HIV positive: 878.2 [99.5]; older HIV negative: 1129.3 [231.6]; younger HIV negative: 1366.5 [172.6] % baseline). Regarding SNP iontophoresis, HIV-positive and older HIV-negative groups showed lower CVC responses than younger HIV-negative group (HIV positive: 1043.0 [164.6]; older HIV-negative: 980.8 [108.3]; younger HIV-negative: 1757.3 [245.1] % baseline). Vasodilatation induced by thermal hyperemia (HIV positive: 1.63 [0.11]; older HIV negative: 1.48 [0.08]; younger HIV negative: 1.85 [0.27] perfusion units/mm Hg) and PORH (HIV positive: 0.374 [0.025]; older HIV negative: 0.326 [0.025]; younger HIV negative: 0.326 [0.037] PU/mm Hg) were similar between all groups. SIDVP was greater in HIV and older healthy groups than younger healthy group (HIV positive: 9.17 [0.42]; older HIV negative: 8.19 [0.43]; younger HIV negative: 6.42 [0.22] m/s).Conclusion: HIV-infected patients under HAART exhibited slight but nonsignificant lower microvas-cular reactivity to pharmacological stimuli and increased arterial stiffness compared to age-matched HIV-negative subjects. Comparison of both HIV-positive and older HIV-negative groups with younger HIV-negative subjects suggests that age plays a major role in microvascular reactivity regardless the HIV-infection.

Influence of nonthermal baroreceptor modulation of heat loss responses during uncompensable heat stress

We evaluated the hypothesis that with increasing levels of hyperthermia, thermal influences would predominate over nonthermal baroreceptor control of cutaneous vascular conductance (CVC) and local sweat rate (LSR). On separate days, eight male participants were positioned in either an upright seated posture (URS) or a 15 degrees head-down tilt (HDT) posture in a thermoneutral condition and during passive heating, until mean body temperature (T(body)) increased by 1.5 degrees C. Hemodynamic [heart rate (HR), cardiac output, mean arterial pressure (MAP)] and thermal responses [T(re), CVC, LSR] were measured continuously. MAP showed a gradual decrease in the early- to mid-stages of heating for both HDT and URS. At a T(body) > 0.6 degrees C, MAP achieved a stable, albeit reduced level from baseline resting for the duration of the heating, whereas MAP decreased significantly throughout the heating period in the URS position (p < 0.001). CVC increased rapidly in the early stages of heating and achieved a stable elevated level in both HDT and URS at the mid-stage of heating (T(body) increase <or= 0.45 degrees C) for the duration of the heating period (i.e., to a T(body) increase of 1.5 degrees C). A similar pattern of response was observed in LSR. A rapid increase in LSR was observed in the early- to mid-stages of heating (T(body) increase <or= 0.75 degrees C), followed by a slower increase until the end of heating. Responses were similar between conditions. We conclude that despite a significant nonthermal drive, as evidenced by a significant difference in MAP between conditions in the late stages of heating, the thermoeffector activity governing CVC and LSR responses are primarily modulated by thermal input.

Effect of functional electrostimulation on impaired skin vasodilator responses to local heating in spinal cord injury

Spinal cord injury (SCI) induces vascular adaptations below the level of the lesion, such as impaired cutaneous vasodilation. However, the mechanisms underlying these differences are unclear. The aim of this study is to examine arm and leg cutaneous vascular conductance (CVC) responses to local heating in 17 able-bodied controls (39 +/- 13 yr) and 18 SCI subjects (42 +/- 8 yr). SCI subjects were counterbalanced for functional electrostimulation (FES) cycling exercise (SCI-EX, n = 9) or control (SCI-C, n = 9) and reanalyzed after 8 wk. Arm and leg skin blood flow were measured by laser-Doppler flowmetry during local heating (42 degrees C), resulting in an axon-reflex mediated first peak, nadir, and a primarily nitric oxide-dependent plateau phase. Data were expressed as a percentage of maximal CVC (44 degrees C). CVC responses to local heating in the paralyzed leg, but also in the forearm of SCI subjects, were lower than in able-bodied controls (P < 0.05 and 0.01, respectively). The 8-wk intervention did not change forearm and leg CVC responses to local heating in SCI-C and SCI-EX, but increased femoral artery diameter in SCI-EX (P < 0.05). Interestingly, findings in skin microvessels contrast with conduit arteries, where physical (in)activity contributes to adaptations in SCI. The lower CVC responses in the paralyzed legs might suggest a role for inactivity in SCI, but the presence of impaired CVC responses in the normally active forearm suggests other mechanisms. This is supported by a lack of adaptation in skin microcirculation after FES cycle training. This might relate to the less frequent and smaller magnitude of skin blood flow responses to heat stimuli, compared with controls, than physical inactivity per se.

Can supine recovery mitigate the exercise intensity dependent attenuation of post-exercise heat loss responses?

Cutaneous vascular conductance (CVC) and sweat rate are subject to non-thermal baroreflex-mediated attenuation post-exercise. Various recovery modalities have been effective in attenuating these decreases in CVC and sweat rate post-exercise. However, the interaction of recovery posture and preceding exercise intensity on post-exercise thermoregulation remains unresolved. We evaluated the combined effect of supine recovery and exercise intensity on post-exercise cardiovascular and thermal responses relative to an upright seated posture. Seven females performed 15 min of cycling ergometry at low- (LIE, 55% maximal oxygen consumption) or high-(HIE, 85% maximal oxygen consumption) intensity followed by 60 min of recovery in either an upright seated or supine posture. Esophageal temperature, CVC, sweat rate, cardiac output, stroke volume, heart rate, total peripheral resistance, and mean arterial pressure (MAP) were measured at baseline, at end-exercise, and at 2, 5, 12, 20, and every 10 min thereafter until the end of recovery. MAP and stroke volume were maintained during supine recovery to a greater extent relative to an upright seated recovery following HIE (p <or= 0.05) and were paralleled by an elevated CVC and sweat rate response (p <or= 0.05). A significantly lower esophageal temperature was subsequently observed when supine throughout recovery (p <or= 0.05). Although we observed a reflex bradycardia and increased stoke volume with supine recovery following LIE, no differences were observed for MAP, CVC, sweat rate or esophageal temperature. Supine recovery attenuates the post-exercise reductions in MAP, CVC, and sweat rate in a manner dependent directly on exercise intensity. This effect is likely attributable to a non-thermal baroreceptor mechanism.