Decrease In Cutaneous Vascular Conductance Research Articles

Acute effects of coffee on skin blood flow and microvascular function

ObjectiveStudies on the acute effects of coffee on the microcirculation have shown contradicting results. This study aimed to investigate if intake of caffeine-containing coffee changes blood flow and microvascular reactivity in the skin. MethodsWe measured acute changes in cutaneous vascular conductance (CVC) in the forearm and the tip of the finger, the microvascular response to transdermal iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) and post-occlusive reactive hyperemia (PORH) in the skin, after intake of caffeinated or decaffeinated coffee. ResultsVasodilatation during iontophoresis of ACh was significantly stronger after intake of caffeinated coffee compared to after intake of decaffeinated coffee (1.26±0.20PU/mmHg vs. 1.13±0.38PU/mmHg, P<0.001). Forearm CVC before and after PORH were not affected by caffeinated and decaffeinated coffee. After intake of caffeinated coffee, a more pronounced decrease in CVC in the fingertip was observed compared to after intake of decaffeinated coffee (−1.36PU/mmHg vs. −0.52PU/mmHg, P=0.002). ConclusionsCaffeine, as ingested by drinking caffeinated coffee acutely improves endothelium-dependent microvascular responses in the forearm skin, while endothelium-independent responses to PORH and SNP iontophoresis are not affected. Blood flow in the fingertip decreases markedly during the first hour after drinking caffeinated coffee compared to decaffeinated coffee.

The influence of Metabo‐ and Baroreceptors on Postexercise Heat Loss

We studied the relative and separate contribution of metabo‐ and baroreflex activity to heat loss during postexercise recovery. Seven males (21 ± 2 years) performed 15 min of running (90% heart rate max) in the heat (35°C). During the 60 min postexercise period, four 1‐min bouts of isometric handgrip exercise (IHG) were followed by 2 min of forearm ischemia (toactivate metaboreceptors, OCC), each separated by 15 min. This was repeated on separate days during a normal seated recovery (CON) and during the application of lower body positive (LBPP, +40 mmHg) or negative (LBNP, ‐20 mmHg) pressure starting at 13 min of recovery. Forearm sweat rate and cutaneous vascular conductance (CVC) were measured continuously. For all conditions CVC returned to pre‐dynamic exercise resting levels at 45 min of recovery (P &gt; 0.05) whereas sweating remained elevated for the duration of recovery (P &lt; 0.05). Relative to pre‐IHG resting CVC was reduced during IHG at 15 min of recovery and subsequently returned to pre‐IHG levels during OCC in CON only. No effect of IHG on CVC was observed for LBPP or LBNP. However LBNP caused an OCC‐induced decrease in CVC from pre‐IHG levels at 15 min of recovery only (P &lt; 0.05). Sweating increased during IHG and remained elevated at similar levels during OCC for all conditions in the final 30 min of recovery (P &lt; 0.05). We show that metaboreceptors influence CVC during the early stages of recovery which is modulated to a certain extent by baroreceptor activity. In contrast, sweating is influenced by metaboreceptor activation in the mid‐to‐late stages of recovery independent of changes in baroreceptor activity. Support: Natural Sciences and Engineering Research of Canada.

Adenosine receptor inhibition attenuates the decrease in cutaneous vascular conductance during whole‐body cooling from hyperthermia

Adenosine has both vasodilatory and vasoconstrictive properties, yet its influence on cutaneous vascular conductance (CVC) during whole-body cooling remains unknown. The present study evaluated the influence of adenosine on reflex cutaneous vasoconstriction. Four microdialysis probes were inserted into the dorsal forearm skin of eight subjects and infused with the following solutions: (i) lactated Ringer solution (CON); (ii) 4 mm theophylline (Theo), a non-selective adenosine receptor antagonist; (iii) 10 mm l-NAME, an inhibitor of nitric oxide synthase; and (iv) combined 4 mm theophylline and 10 mm l-NAME (Theo + l-NAME). Subjects subsequently donned a water-perfusion garment. Following a thermoneutral baseline period, the suit was perfused with water at 10°C for 20 min (Cooling 1). The suit was then perfused with water at 49°C for 45 min (Heating), followed by a second cooling period of 20 min using 10°C water (Cooling 2). Cutaneous blood flow (laser-Doppler) was measured over each microdialysis probe and used to calculate CVC as a percentage of the maximum determined by sodium nitroprusside infusion and local heating. Cutaneous vascular conductance was significantly elevated at the Theo site relative to CON following Cooling 1 (18 ± 6 versus 8 ± 2%; P = 0.01) and Cooling 2 (27 ± 11 versus 14 ± 5%; P = 0.022). Likewise, CVC at the Theo + l-NAME site remained greater compared with l-NAME after Cooling 1 (13 ± 4 versus 7 ± 3%; P = 0.030) and Cooling 2 (15 ± 3 versus 9 ± 2%; P = 0.009). The present findings demonstrate that non-selective antagonism of adenosine receptors attenuates the decrease in cutaneous vascular conductance during whole-body cooling from hyperthermia.

Sildenafil Increases Digital Skin Blood Flow During All Phases of Local Cooling in Primary Raynaud's Phenomenon

Digital skin vasoconstriction on local cooling is exaggerated in primary Raynaud's phenomenon (RP) as compared with controls. A significant part of such vasoconstriction relies on the inhibition of the nitric oxide (NO) pathway. We tested the effect of the phosphodiesterase 5 (PDE5) inhibitor sildenafil, which potentiates the effect of NO, on skin blood flow. We recruited 15 patients with primary RP, performing local cooling without sildenafil (day 1), after a single oral dose of 50 mg (day 2), and after a dose of 100 mg (day 3). Skin blood flow, skin temperature, and arterial pressure were recorded, and data were expressed as cutaneous vascular conductance (CVC). Sildenafil at 100 mg, but not 50 mg, significantly lessened the cooling-induced decrease in CVC. It also increased resting CVC and skin temperature. These data suggest that 100 mg sildenafil improves digital skin perfusion during local cooling in primary RP. The benefit of sildenafil "as required" should be confirmed in a randomized, controlled trial.

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

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.

The involvement of nitric oxide in the cutaneous vasoconstrictor response to local cooling in humans

Cutaneous vascular conductance (CVC) declines in response to local cooling (LC). Previous work indicates that at least part of the vasoconstrictor response to LC may be through an inhibitory effect on nitric oxide synthase (NOS) activity. In this study we further tested that notion. A total of eight (6 male, 2 female) subjects participated (Part 1 n = 7; Part 2 n = 5, 4 of whom participated in Part 1). Skin blood flow was monitored by laser-Doppler flowmetry. Control of local skin and body temperatures was achieved with Peltier cooler/heater probe holders and water perfused suits, respectively. Microdialysis fibres were inserted aseptically. Saline, L-NAME (20 mM; to inhibit NOS activity) and sodium nitroprusside (SNP 10 microM) were infused by microdialysis. Bretylium tosylate (BT), to block adrenergic function, was administered by iontophoresis. CVC was calculated from blood flow and blood pressure. Part 1 was designed to determine the relative roles of the NO and the adrenergic systems. The infusion of L-NAME elicited a 35 +/- 4% decrease in CVC at the L-NAME and BT + L-NAME sites (P < 0.05); subsequent slow LC (34-24 degrees C) for 35 min caused a significant (P < 0.05) decrease in CVC at control sites (68 +/- 4%) and at the BT treated sites (39 +/- 5%). LC caused a further 23 +/- 5% of initial baseline decrease in CVC at the L-NAME treated sites (P < 0.05). Importantly, CVC at the BT + L-NAME sites was unaffected by LC (P > 0.05). Part 2 was designed to test whether LC influences were specific to the NOS enzymes. Two sites were pretreated with both BT and L-NAME. After 50 min, SNP was added as an NO donor to restore baseline CVC at one site. The same LC process as in Part 1 was applied. There was a 24 +/- 10% decrease (P < 0.05) in CVC at sites with baseline CVC restored, while, as in Part 1, there was no change (P > 0.05) at sites treated with BT + L-NAME only. These data suggest that the vasoconstriction with slow LC is due to a combination of increased noradrenaline release and decreased activity of both NOS per se and of process(es) downstream of NOS.

Cutaneous Venoarteriolar And Baroreflex-mediated Responses In Post-exercise Orthostatic Tolerant And Intolerant Endurance Athletes

In response to post-exercise orthostasis cutaneous vascular conductance (CVC) decreases, indicating maintenance of the ability to vasoconstrict after exercise even though CVC remains higher then pre-exercise values. Whether the cutaneous vasoconstriction is a result of a cutaneous venoarteriolar or baroreflex-mediated response is unclear. Whatever the mechanisms, the opposing thermoregulatory and blood pressure regulatory influences, which increase and decrease CVC respectively, have implications for post-exercise thermoregulation, hypotension and orthostatic tolerance. PURPOSE To determine the cutaneous venoarteriolar and baroreflex-mediated responses in post-exercise orthostatic intolerance and orthostatic intolerance. METHODS Twenty young, endurance-trained athletes (VO2peak, 66.3±1.5 ml·kg−1·min−1) participated. The dependent variables were measured before exhaustive incremental exercise on a cycle ergometer and between 10 and 46 minutes of recovery. The cutaneous venoarteriolar-mediated response was represented by a decrease in CVC, measured by laser-Doppler flowmetry, of the forearm and finger when the hand was lowered 50cm below the level of the heart for 6 minutes in the supine posture. The cutaneous baroreflex-mediated response was represented by a decrease in CVC of the forearm and finger at heart level during 6 minutes of standing. Cutaneous vascular conductance was calculated as flux/mean arterial pressure and scaled as % of maximal CVC (skin surrounding the laser-Doppler probes heated to 42 °C for 30 minutes). Pre- and post-exercise responses were compared between post-exercise episodes of orthostatic intolerance (n=9) and orthostatic tolerance (n=11). RESULTS There was a greater reduction in cutaneous venoarteriolar-mediated response from the pre-exercise to post-exercise period in orthostatic intolerance compared to orthostatic tolerance (forearm: −17±4 vs. –5±4% max, p=0.03; finger: −19±7 vs. –8±4% max, p=0.03). In the forearm this greater reduction was partly offset by an increase in the cutaneous baroreflex-mediated response in the post-exercise compared to pre-exercise period (+14±8% max, p=0.001). In addition, during the prodromal period preceding orthostatic intolerance, the cutaneous baroreflex-mediated response significantly increased up to the point of pre-syncope compared to the final 2 minutes of orthostatic tolerance (forearm, p=0.05; finger, p=0.01). CONCLUSION Inadequacies of thermoregulation post-exercise may be postulated as the underlying cause of orthostatic intolerance rather than baroreflex-mediated regulation of blood pressure.

Cutaneous vascular responses to isometric handgrip exercise during local heating and hyperthermia

The dramatic increase in skin blood flow and sweating observed during heat stress is mediated by poorly understood sympathetic cholinergic mechanisms. One theory suggests that a single sympathetic cholinergic nerve mediates cutaneous active vasodilation (AVD) and sweating via cotransmission of separate neurotransmitters, because AVD and sweating track temporally and directionally when activated during passive whole body heat stress. It has also been suggested that these responses are regulated independently, because cutaneous vascular conductance (CVC) has been shown to decrease, whereas sweat rate increases, during combined hyperthermia and isometric handgrip exercise. We tested the hypothesis that CVC decreases during isometric handgrip exercise if skin blood flow is elevated using local heating to levels similar to that induced by pronounced hyperthermia but that this does not occur at lower levels of skin blood flow. Subjects performed isometric handgrip exercise as CVC was elevated at selected sites to varying levels by local heating (which is independent of AVD) in thermoneutral and hyperthermic conditions. During thermoneutral isometric handgrip exercise, CVC decreased at sites in which blood flow was significantly elevated before exercise (-6.5 +/- 1.8% of maximal CVC at 41 degrees C and -10.5 +/- 2.0% of maximal CVC at 43 degrees C; P < 0.05 vs. preexercise). During isometric handgrip exercise in the hyperthermic condition, an observed decrease in CVC was associated with the level of CVC before exercise. Taken together, these findings argue against withdrawal of AVD to explain the decrease in CVC observed during isometric handgrip exercise in hyperthermic conditions.

Influence of the Menstrual Cycle and Sex on the Skin Blood Flow Response to Tilting

0266 Women have decreased orthostatic tolerance compared with men, and anecdotal evidence suggests women are most susceptible to orthostatic intolerance in warm environments. Estrogen and progesterone are known to Influence the regulation of skin blood flow, and thus may impact the responses to an orthostatic challenge. PURPOSE: To examine sex differences and the Influence of the menstrual cycle on cutaneous vascular conductance (CVC) during orthostatic challenges in thermoneutral and heat stress conditions. METHODS: Three women not currently taking oral contraceptives (24±7 years) and 4 males (24±4 years) have been studied. Female subjects were studied during their early follicular, ovulatory, and midluteal menstrual cycle phases. Male subjects were studied twice within a 2–4 week period. Subjects underwent 2 head up tilt tests on an automatic tilt table. Tilts consisted of progressive 5 minute stages at 15°, 30°, 45° and 60° during thermoneutral conditions and again after a 0.5° C increase in core body temperature via whole body heating. An index of skin blood flow (RBC Flux) was measured by laser-Doppler flowmetery and (CVC) was calculated as RBC Flux/MAP. RESULTS: We observed similar decreases in CVC with increasing orthostatic stress in the thermoneutral condition between men and women in the early follicular and ovulatory phases. However, we observed a slight increase in CVC from baseline during the midluteal phase. During heat stress, CVC increased similarly in both sexes, but increased the most in the midluteal phase. When tilting was combined with heat stress the greatest decrease in CVC was observed during the midluteal phase. CONCLUSION: These preliminary data suggest the skin blood flow response to an orthostatic challenge differs in the midluteal verses other phases of the menstrual cycle. Supported by AHA grant 0265260Z

Influence of the Menstrual Cycle and Sex on the Skin Blood Flow Response to Tilting

0266 Women have decreased orthostatic tolerance compared with men, and anecdotal evidence suggests women are most susceptible to orthostatic intolerance in warm environments. Estrogen and progesterone are known to Influence the regulation of skin blood flow, and thus may impact the responses to an orthostatic challenge. PURPOSE: To examine sex differences and the Influence of the menstrual cycle on cutaneous vascular conductance (CVC) during orthostatic challenges in thermoneutral and heat stress conditions. METHODS: Three women not currently taking oral contraceptives (24±7 years) and 4 males (24±4 years) have been studied. Female subjects were studied during their early follicular, ovulatory, and midluteal menstrual cycle phases. Male subjects were studied twice within a 2–4 week period. Subjects underwent 2 head up tilt tests on an automatic tilt table. Tilts consisted of progressive 5 minute stages at 15°, 30°, 45° and 60° during thermoneutral conditions and again after a 0.5° C increase in core body temperature via whole body heating. An index of skin blood flow (RBC Flux) was measured by laser-Doppler flowmetery and (CVC) was calculated as RBC Flux/MAP. RESULTS: We observed similar decreases in CVC with increasing orthostatic stress in the thermoneutral condition between men and women in the early follicular and ovulatory phases. However, we observed a slight increase in CVC from baseline during the midluteal phase. During heat stress, CVC increased similarly in both sexes, but increased the most in the midluteal phase. When tilting was combined with heat stress the greatest decrease in CVC was observed during the midluteal phase. CONCLUSION: These preliminary data suggest the skin blood flow response to an orthostatic challenge differs in the midluteal verses other phases of the menstrual cycle. Supported by AHA grant 0265260Z

Blood distribution adaptations in paraplegics during posture changes: peripheral and central reflex responses.

The veno-arteriolar reflex (VAR) in spinal-cord-injured subjects (SCI) has been attributed little interest, although it might contribute substantially to their blood redistribution. This peripheral reflex response, which is based on an axon reflex, consists of a reduction in limb blood flow following an increase in venal transmural pressure. The purpose of the present investigation was to assess the peripheral and central cardiovascular adaptations of paraplegics with high (HP) and low (LP) spinal lesions to subsequent, passive posture changes involving leg dependency and upright sitting, and to compare them to able-bodied (AB) subjects. Lower-limb cutaneous vascular conductance (CVC) was evaluated from skin blood flow measurements (laser Doppler flowmetry) taken from the dorsal foot, and from ankle blood pressure. Cardiac stroke volume, heart rate and myocardial performance were assessed using impedance cardiography and brachial blood pressure. During leg dependency, a significant vasoconstriction was noted in all three groups. The initial decrease in CVC was higher in HP (-76.82%) than in AB (-45.82%), the values for LP (-67.08%) lying in between these two (significant group x time interaction: F = 2.832; P = 0.042). There were no differences for parameters of central hemodynamics. No between-group differences were noted in any parameter tested during upright sitting. CVC remained at a similar low level as compared to leg dependency, stroke volume decreased, heart rate and blood pressure increased, and myocardial performance remained constant. The present results suggest that paraplegics have a peripheral VAR in their paralyzed lower limbs, and that this contributes to their cardiovascular stability.

Competition between cutaneous vasodilator and vasoconstrictor reflexes in man.

A two-part experiment was carried out on seven men to determine whether skin will respond to increased neurogenic vasoconstrictor activity during heating. The latter was induced by lower body negative pressure of -50 mm Hg applied for 5 of each 15 min in 12 studies with constant, neutral skin temperature (32.2-34.4 C) in a 40-min control period and with skin temperature held at 38 C for 40-70 min. We conclude that during heating, skin retains the ability to vasoconstrict but that this vasoconstriction cannot completely override heat-induced vasodilatation.