Habitation and recovery of vascular responses in calf and forearm and of the level of pain sensation during the cold pressor test in man

Forearm and calf blood flow were measured using a mercury-in-silastic gauge during immersion of one foot in water at 4 degrees C. The subjects were asked to assess the level of pain on a scale 0-10. The effects of one session of repeated immersions on the vascular response in the calf, forearm and on subjective pain sensation were studied. In 6 of the 14 subjects vasodilatation was elicited in both forearm and calf during the first immersion. During the first session the vasodilation diminished, while subjective pain sensation remained at the level of 7 on the scale. In 4 subjects vasoconstriction in both calf and forearm occurred during the first immersion. During repeated immersions forearm vasoconstriction subsided, while in the calf it remained at the same level. The level of the subjective pain sensation diminished from 7.5 to 5 in 1 subject. Repeated immersions in six to ten daily sessions led to reduction of vasodilatation in calf and forearm while there was a small change in the pain sensation, i.e. reduction from the level of 6.9 to 5.7 (P less than 0.01). In subjects in whom vasoconstriction in forearm and calf was observed no clear trend in vascular responses was observed during the repeated daily sessions while the pain sensation in 1 subject was reduced from 6 to 4.8. In 3 subjects the change of vascular responses was different in the forearm and calf.(ABSTRACT TRUNCATED AT 250 WORDS)     

Habituation of the cold pressor response in normo- and hypertensive human subjects

The changes in cardiovascular response to repeated cold-pressor test were studied in young normotensive and in young hypertensive subjects. The cold stimulus consisted of immersing one foot in cold water (4 degrees C) for 60 s. Non-invasive methods were used to record the cardiovascular responses: blood flow of the calf was measured using venous occlusion plethysmography, arterial blood pressure with sphygmomanometery, heart rate with electrocardiography. The vascular conductance level in the calf was higher in hypertensive subjects than in normotensives. The difference remained throughout the series of 6 daily experiments. In both hypertensive and normotensive groups of subjects some individuals responded to the cold stimulus with vasodilatation in the calf muscles, others with vasoconstriction. In the hypertensives blood flow increased more and habituation was only transient with a strong tendency for the vasodilatory response to recover, while in normotensives habituation was rapid and complete. Vasoconstrictor responses showed no signs of reduction. The blood pressure increases were larger in hypertensives and remained unaltered within the period of repeated tests (6 days). There was not significant difference between the heart rate changes in the two groups of subjects. It is concluded that the vasculature of the calf shows lower tone and is more labile during the early stage of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)     

Calf blood flow and vascular resistance during reactive hyperaemia in young athletes and trained middle-aged subjects

The effect of training on dilatation capacity in the lower limbs was evaluated by studying the blood flow and vascular resistance in the calf in 10 young athletes aged 19-29 years and 15 trained middle-aged subjects aged 52-58 years during post-ischaemic reactive hyperaemia. The control groups comprised untrained subjects of approximately the same ages, i.e. 16 men aged 18-29 and 37 aged 40-60. The calf blood flow as determined plethysmographically and the blood pressure was measured on the arm by auscultation. Vascular resistance was calculated from the mean blood pressure and from the maximal calf blood flow measured during hyperaemia. A significantly higher maximal blood flow and significantly lower resistance in the calf were found in young athletes than in untrained subjects. In athletes, the flow debt was significantly overpaid. In middle-aged subjects, the effect of training was manifested only in significant overpayment of the flow debt, while vascular resistance and the maximal blood flow were the same as in the controls. It can be concluded from these findings that significant improvement of vasodilatation ability in association with training occurs primarily in young subjects. The findings also correspond to the known ability of young athletes to give a higher maximal performance than veteran athletes.     

Role of atrial natriuretic peptide and urinary cGMP in the natriuretic and diuretic response to central hypervolemia in normal human subjects

The response of plasma atrial natriuretic peptide (ANP) and urinary cGMP excretion to central hypervolemia induced by water immersion was assessed twice in five healthy male subjects, once while immersed in water to the neck for 3 h and again on a control day. Plasma ANP and urinary cGMP were measured by radioimmunoassay. Compared with the control day, overall change in plasma ANP on the immersion day was significant (p less than 0.05). In response to water immersion, plasma ANP increased from a base-line level of 13.2 +/- 3.1 (mean +/- SEM) to 24.2 +/- 5.5 pg/mL by 0.5 h of immersion and was sustained at that level throughout the immersion period. Plasma ANP returned to the base-line level at 1 h postimmersion. Urinary cGMP excretion increased significantly by 1 h of immersion and was sustained at that level throughout water immersion and 1 h postimmersion (p less than 0.05). During water immersion urine flow, urinary sodium and potassium excretion, free water clearance, and osmolar clearance increased while plasma renin activity, serum aldosterone, and blood pressure fell; all changes were significant (p less than 0.05). Creatinine clearance and hematocrit did not show any significant changes. These data suggest that an increase in plasma ANP may contribute to the natriuretic and diuretic response to central hypervolemia, and that the measurement of urinary cGMP may be a valuable marker of ANP biological responsiveness.     

Finger and forearm vasodilatatory changes after local cold acclimation

To determine the vascular changes induced by local cold acclimation, post-ischaemia and exercise vasodilatation were studied in the finger and the forearm of five subjects cold-acclimated locally and five non-acclimated subjects. Peak blood flow was measured by venous occlusion plethysmography after 5 min of arterial occlusion (PBFisc), after 5 min of sustained handgrip at 10% maximal voluntary contraction (PBFexe), and after 5 min of both treatments simultaneously (PBFisc + exe). Each test was performed at room temperature (25 degrees C, SE 1 C) (non-cooled condition) and after 5 min of 5 degrees C cold water immersion (cooled condition). After the cold acclimation period, the decrease in skin temperature was more limited in the cold-acclimated compared to the non-acclimated (P less than 0.01). The PBFisc was significantly reduced in the cooled condition only in the cold-acclimated subjects (finger: 8.4 ml.100 ml-1.min-1, SE 1.1, P less than 0.01; forearm: 5.8 ml.100 ml-1.min-1, SE 1.5, P less than 0.01) compared to the non-cooled condition. Forearm PBFexe was significantly decreased in the cooled condition only in the cold-acclimated subjects (non-cooled: 7.4 ml.100 ml-1.min-1, SE 1.2; cooled: 3.9 ml.100 ml-1.min-1, SE 2.6, P less than 0.05) indicating that muscle blood flow was also reduced.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of local cooling on skin temperature and blood flow of men in Antarctica

Alterations to the finger skin temperature (Tsk) and blood flow (FBF) before and after cold immersion on exposure to an Antarctic environment for 8 weeks were studied in 64 subjects. There was a significant fall in Tsk and increase in finger blood flow after 1 week of Antarctic exposure. The Tsk did not further change even after 8 weeks of stay in Antarctica but a significant increase in FBF was obtained after 8 weeks. The cold immersion test was performed at non-Antarctic and Antarctic conditions by immersing the hand for 2 min in 0–4° C cold water. In the non-Antarctic environment the Tsk and FBF dropped significantly (P < 0.001) indicating a vasoconstriction response. Interestingly after 8 weeks of stay in Antarctic conditions, the skin temperature dropped (P < 0.001) but the cold induced fall in FBF was inhibited. Based on these observations it may be hypothesized that continuous cold exposure in Antarctica results in vasodilatation, which overrides the stronger vasoactive response of acute cold exposure and thus prevents cold injuries.     

Mechanisms of blood pressure regulation that differ in men repeatedly exposed to high-G acceleration

The purpose of this study was to test the hypothesis that repeated exposure to high acceleration (G) would be associated with enhanced functions of specific mechanisms of blood pressure regulation. We measured heart rate (HR), stroke volume (SV), cardiac output (), mean arterial blood pressure, central venous pressure, forearm and leg vascular resistance, catecholamines, and changes in leg volume (%DeltaLV) during various protocols of lower body negative pressure (LBNP), carotid stimulation, and infusions of adrenoreceptor agonists in 10 males after three training sessions on different days over a period of 5-7 days using a human centrifuge (G trained). These responses were compared with the same measurements in 10 males who were matched for height, weight, and fitness but did not undergo G training (controls). Compared with the control group, G-trained subjects demonstrated greater R-R interval response to equal carotid baroreceptor stimulation (7.3 +/- 1.2 vs. 3.9 +/- 0.4 ms/mmHg, P = 0.02), less vasoconstriction to equal low-pressure baroreceptor stimulation (-1.4 +/- 0.2 vs. -2.6 +/- 0.3 U/mmHg, P = 0.01), and higher HR (-1.2 +/- 0.2 vs. -0.5 +/- 0.1 beats. min(-1). mmHg(-1), P = 0.01) and alpha-adrenoreceptor response (32.8 +/- 3.4 vs. 19.5 +/- 4.7 U/mmHg, P = 0.04) to equal dose of phenylephrine. During graded LBNP, G-trained subjects had less decline in and SV, %DeltaLV, and elevation in thoracic impedance. G-trained subjects also had greater total blood (6,497 +/- 496 vs. 5,438 +/- 228 ml, P = 0.07) and erythrocyte (3,110 +/- 364 vs. 2,310 +/- 96 ml, P = 0.06) volumes. These results support the hypothesis that exposure to repeated high G is associated with increased capacities of mechanisms that underlie blood pressure regulation.     

Peripheral blood flow during rewarming from mild hypothermia in humans

During the initial stages of rewarming from hypothermia, there is a continued cooling of the core, or after-drop in temperature, that has been attributed to the return of cold blood due to peripheral vasodilatation, thus causing a further decrease of deep body temperature. To examine this possibility more carefully, subjects were immersed in cold water (17 degrees C), and then rewarmed from a mildly hypothermic state in a warm bath (40 degrees C). Measurements of hand blood flow were made by calorimetry and of forearm, calf, and foot blood flows by straingauge venous occlusion plethysmography at rest (Ta = 22 degrees C) and during rewarming. There was a small increase in skin blood flow during the falling phase of core temperature upon rewarming in the warm bath, but none in foot blood flow upon rewarming at room air, suggesting that skin blood flow seems to contribute to the after-drop, but only minimally. Limb blood flow changes during this phase suggest that a small muscle blood flow could also have contributed to the after-drop. It was concluded that the after-drop of core temperature during rewarming from mild hypothermia does not result from a large vasodilatation in the superficial parts of the periphery, as postulated. The possible contribution of mechanisms of heat conduction, heat convection, and cessation of shivering thermogenesis were discussed.     

Head-down bed rest alters sympathetic and cardiovascular responses to mental stress

Astronauts usually work under much mental stress. However, it is unclear how and whether or not an exposure to microgravity affects physiological response to mental stress in humans. To examine effects of microgravity on vasomotor sympathetic and peripheral vasodilator responses to mental stress, we performed 10 min of mental arithmetic (MA) before and after 14 days of 6 degrees head-down bed rest (HDBR), a ground-based simulation of spaceflight. Total muscle sympathetic nerve activity (MSNA, measured by microneurography) slightly increased during MA before HDBR, and this increase was augmented after HDBR. Calf blood flow (measured by venous occlusion plethysmography) increased and calf vascular resistance (calculated by dividing mean blood pressure by calf blood flow) decreased during MA before HDBR, but these responses were abolished after HDBR. Increases in heart rate and mean blood pressure during MA were not different between before and after HDBR. These findings suggest that HDBR augmented vasomotor sympathoexcitation but attenuated vasodilatation in the calf muscle in response to mental stress.     

Repeated increases in blood flow, independent of exercise, enhance conduit artery vasodilator function in humans

This study aimed to determine the importance of repeated increases in blood flow to conduit artery adaptation, using an exercise-independent repeated episodic stimulus. Recent studies suggest that exercise training improves vasodilator function of conduit arteries via shear stress-mediated mechanisms. However, exercise is a complex stimulus that may induce shear-independent adaptations. Nine healthy men immersed their forearms in water at 42°C for three 30-min sessions/wk across 8 wk. During each session, a pneumatic pressure cuff was inflated around one forearm to unilaterally modulate heating-induced increases in shear. Forearm heating was associated with an increase in brachial artery blood flow (P<0.001) and shear rate (P<0.001) in the uncuffed forearm; this response was attenuated in the cuffed limb (P<0.005). Repeated episodic exposure to bilateral heating induced an increase in endothelium-dependent vasodilation in response to 5-min ischemic (P<0.05) and ischemic handgrip exercise (P<0.005) stimuli in the uncuffed forearm, whereas the 8-wk heating intervention did not influence dilation to either stimulus in the cuffed limb. Endothelium-independent glyceryl trinitrate responses were not altered in either limb. Repeated heating increases blood flow to levels that enhance endothelium-mediated vasodilator function in humans. These findings reinforce the importance of the direct impacts of shear stress on the vascular endothelium in humans.     

The interstitial fluid content in working muscle modifies the cardiovascular response to exercise

The volume of interstitial fluid in the limbs varies considerably, due to hydrostatic effects. As signals from working muscle, responsible for much of the cardiovascular drive, are assumed to be transmitted in this compartment, blood pressure and heart rate could be affected by local or systemic variations in interstitial hydration. Using a special calf ergometer, eight male subjects performed rhythmic aerobic plantar flexions in a supine position with dependent calves for periods of 7 min. During exercise heart rate, blood pressure, oxygen uptake (VO2) and blood lactate concentrations were measured in two different tests, one before and after interstitial calf dehydration through limb elevation for 25 min, compared to the other, a control with unaltered fluid volume in a maintained working position. Impedance plethysmography showed calf volume to be stabilized in the control position. Leg elevation by passive hip flexion to 90 degrees resulted in a fast (vascular) volume decrease lasting less than 2 min, followed by a slow linear fluid loss from the interstitial compartment. Then, when returned to the control position, adjustment of vascular volume was completed within 2 min and exercise could be performed with dehydration remaining in the interstitium only. Cardiovascular response was identical at the start of both tests. However, exercising with dehydrated calves elicited a significantly larger increase in heart rate compared to the control, whereas VO2 was identical. The blood pressure response was shown to be only slightly enhanced. Structural interstitial features varying with hydration, most likely chemical or mechanical ones, may have been responsible for this amplification of signals.     

Arterial distensibility: acute changes following dynamic exercise in normal subjects

The time course of acute changes in large artery distensibility immediately and for 60 min following maximum treadmill exercise in normal subjects was characterized by simultaneously measuring upper and lower limb pulse wave velocity (PWV). A new oscillometric technique was used, which has proven to be sensitive to changes in distensibility induced by acute changes in vascular tone independently of blood pressure. The observed changes in PWV are attributable to changes in vascular tone corresponding to recovery from a systemic net constrictor response and a local net dilator response to exercise with persisting postexercise vasodilatation. They are inadequately explained by associated changes in blood pressure and cannot be attributed to changes in heart rate or viscosity. Modeled as a system of n coupled linear differential equations, the minimum (and adequate) order required to reproduce these patterns was n = 1 for the upper and n = 2 for the exercising lower limb. The economy of the solution suggests entrainment among the multiple interactive mechanisms governing vasomotor control.     

On the reliability of the Penaz cuff during systemic and local fingertip vasodilatation at rest and in exercise

To compare the readings of blood pressure by the Riva-Rocci (RR) method with those of peripheral arterial pressure (PAP) as recorded by the Finapres (FP) device, exercise was performed by six male subjects on a cycle ergometer at a constant exercise intensity of 140 W. In addition, forearm volume was determined by impedance plethysmography. At rest, systolic FP values exceeded RR values by greater than or equal to 10 mmHg. During 60-min exercise both values at first increased almost in parallel with each other. While RR reached a plateau after 3 min, FP then started to decrease continuously up to the 10th min and finally stabilized at 20-30 mmHg below RR. The impedance values showed a similar declining slope, indicating vasodilatation. To separate the effects of sympathetic drive from heat elicited vasodilatation, a second experimental series was performed with ischaemic static calf exercise (5 min, 90 N), since this increases the sympathetic tone but prevents systemic heat distribution. In contrast to findings reported from intra-arterial measurements, no exercise effect on the pulse pressure amplification was obtained. However, the heating of one fingertip distal to the FP-cuff led to a significant decrease in PAP compared to the control recording made simultaneously from the other hand. It was concluded that heat induced vasodilatation may make FP unrepresentative of systemic blood pressure, in particular during exercise. Moreover, the FP-cuff seemed to induce substantial vasoconstriction due to venous occlusion. The FP method would therefore be useful for monitoring continuously systemic blood pressure if no (dilative) vasomotor changes occurred or their ranges and time courses were known sufficiently well.     

Serotonin induced vasodilatation in the human forearm is antagonized by the selective 5-HT3 receptor antagonist ICS 205-930

The role of 5-HT3 receptors in the biphasic vasodilator response to serotonin (5-hydroxytryptamine; 5-HT) was investigated in the forearm of 7 young healthy volunteers (aged 22-32 years). Single dose infusions of 5-HT (1 ng/kg/min) and of acetylcholine (ACh, 500 ng/kg/min) were administered into the brachial artery. Subsequently combined infusions of 5-HT together with the selective 5-HT3 receptor antagonist ICS 205-930 (350 and 700 ng/kg/min), and ACh together with ICS 205-930 (700 ng/kg/min) were given. After a pause of at least 1 hour the single infusions of 5-HT and ACh were repeated. Subsequently, 5-HT and ACh were infused together with atropine (100 ng/kg/min). Forearm blood flow (FBF) was measured by R-wave triggered venous occlusion plethysmography. Heart rate (HR) and i.a. blood pressure (BP) were recorded semi-continuously. None of the drugs in the doses used did induce systemic hemodynamic effects. After an initial rapid transient increase in FBF of 316 +/- 55%, 5-HT elicited a persistent increase in FBF of 90 +/- 22% (mean +/- SEM, p less than 0.05 for both). ACh induced a monophasic vasodilatation of 475 +/- 123% (p less than 0.05). Both the initial transient and the persistent dilatator response to 5-HT were attenuated by ICS 205-930 350 ng/kg/min (p = 0.057, n = 5) and 700 ng/kg/min (p less than 0.05, n = 7). The highest dose of ICS 205-930 did not significantly influence the dilatator response to ACh. Atropine abolished the ACh induced vasodilatation (p less than 0.05), but did not influence the biphasic dilatator response to 5-HT. Thus the 5-HT induced biphasic vasodilatation was antagonized by ICS 205-930, indicating that this response was mediated by 5-HT3 receptor activation. The fact that atropine did not influence the vascular response to 5-HT suggests that 5-HT did not induce vascular relaxation indirectly by the release of ACh from cholinergic nerve endings.     

The effects of support deprivation and stimulation of the foot support zones on the lateral stiffness and electromyogram of the resting calf muscles

The lateral stiffness and electromyogram characteristics of the resting calf flexor and extensor muscles have been studied in 18 subjects during a seven-day immersion with and without mechanical stimulation of the foot support zones. It has been shown that as early as day 1 of support deprivation, the lateral stiffness steadily decreases in the m. soleus and, in contrast, drastically increases in the m. tibialis anterior. A mechanical stimulation of the foot support zones decreases the rate and degree of the changes observed in both muscles. The tight correlation of the changes in the lateral stiffness with the muscle activity suggests a significant dependence of these changes on the electromyogram characteristics at rest.     

Respiratory, circulatory and neuropsychological responses to acute hypoxia in acclimatized and non-acclimatized subjects

Respiratory, circulatory and neuropsychological responses to stepwise, acute exposure at rest to simulated altitude (6,000 m) were compared in ten acclimatized recumbent mountaineers 24 days, SD 11 after descending from Himalayan altitudes of at least 4,000 m with those found in ten non-acclimatized recumbent volunteers. The results showed that hypoxic hyperpnoea and O2 consumption at high altitudes were significantly lower in the mountaineers, their alveolar gases being, however, similar to those of the control group. In the acclimatized subjects the activation of the cardiovascular system was less marked, systolic blood pressure, pulse pressure, heart rate and thus (calculated) cardiac output being always lower than in the controls; diastolic blood pressure and peripheral vascular resistance, however, were maintained throughout in contrast to the vasomotor depression induced by central hypoxia which occurred in the non-acclimatized subjects at and above 4,000 m [alveolar partial pressure of O2 less than 55-50 mmHg (7.3-6.6 kPa)]. It was concluded that in the acclimatized subjects at high altitude arterial vasodilatation and neurobehavioural impairment, which in the non-acclimatized subjects reflect hypoxia of the central nervous system, were prevented; that acclimatization to high altitude resulted in a significant improvement of respiratory efficiency and cardiac economy, and that maintaining diastolic blood pressure (arterial resistance) at and above 4,000 m may represent a useful criterion for assessing hypoxia acclimatization.     

Venous occlusion to the lower limb attenuates vasoconstriction in the nonexercised limb during posthandgrip muscle ischemia.

We investigated the effects of increases in calf volume on cardiovascular responses during handgrip (HG) exercise and post-HG exercise muscle ischemia (PEMI). Seven subjects completed two trials: one control (no occlusion) and one venous occlusion (VO) session. Both trials included a baseline measurement followed by 15 min of rest (REST), 2 min of HG, and 2 min of PEMI. VO was applied at 100 mmHg via cuffs placed around both distal thighs during REST, HG, and PEMI. Mean arterial pressure, heart rate, forearm blood flow (FBF) in the nonexercised arm, and forearm vascular resistance (FVR) in the nonexercised arm (FVR) were measured. During REST and HG, there were no significant differences between trials in all parameters. During PEMI in the control trial, mean arterial pressure and FVR were significantly greater and FBF was significantly lower than baseline values (P < 0.05 for each). In contrast, in the VO trial, FBF and FVR responses were different from control responses. In the VO trial, FBF was significantly greater than in the control trial (4.7 +/- 0.5 vs. 2.5 +/- 0.3 ml x 100 ml(-1) x min(-1), P < 0.05) and FVR was significantly lower (28.0 +/- 4.8 vs. 49.1 +/- 4.6 units, respectively, P < 0.05). These results indicate that increases in vascular resistance in the nonexercised limb induced by activation of the muscle chemoreflex can be attenuated by increases in calf volume.     

Interstitial transudation with postural changes in man]

Starling-Landis concepts of formation of interstitial fluids are in agreement with measurements of calf volume in normal young women, in horizontal recumbency or after horizontal immersion. The volume of the calf is reduced when the hydrostatic pressure of the blood column is diminished under the phlebostatic level and when the external pressure is increased by the hydrostatic pressure of the water bath.     

Thermal, cardiac and adrenergic responses to repeated local cooling

The aim of this study was to ascertain whether repeated local cooling induces the same or different adaptational responses as repeated whole body cooling. Repeated cooling of the legs (immersion into 12 degrees C water up to the knees for 30 min, 20 times during 4 weeks = local cold adaptation - LCA) attenuated the initial increase in heart rate and blood pressure currently observed in control subjects immersed in cold water up to the knees. After LCA the initial skin temperature decrease tended to be lower, indicating reduced vasoconstriction. Heart rate and systolic blood pressure appeared to be generally lower during rest and during the time course of cooling in LCA humans, when compared to controls. All these changes seem to indicate attenuation of the sympathetic tone. In contrast, the sustained skin temperature in different areas of the body (finger, palm, forearm, thigh, chest) appeared to be generally lower in LCA subjects than in controls (except for temperatures on the forehead). Plasma levels of catecholamines (measured 20 and 40 min after the onset of cooling) were also not influenced by local cold adaptation. Locally cold adapted subjects, when exposed to whole body cold water immersion test, showed no change in the threshold temperature for induction of cold thermogenesis. This indicates that the hypothermic type of cold adaptation, typically occurring after systemic cold adaptation, does not appear after local cold adaptation of the intensity used. It is concluded that in humans the cold adaptation due to repeated local cooling of legs induces different physiological changes than systemic cold adaptation.     

前列环素参与低氧,高二氧化碳脑血管张力调节

本工作是在初生小牛基底动脉血管条上,用前列环素合成酶抑制剂—消炎痛（Ｉｎｄｏｍｅｔｈａｃｉｎ）研究前列环素及内皮细胞在低氧高二氧化碳脑血管扩张机制中的作用。实验结果表明,消炎痛对常氧下脑血管张力没有影响,但可抑制低氧高二氧化碳引起的脑血管扩张反应。去除内皮细胞后低氧、高二氧化碳扩张脑血管的作用显著减小,此时再给予消炎痛对血管张力无明显作用。由此提示,前列环素和内皮细胞参与低氧,高二氧化碳的脑血管扩张作用,而前列环素是来源于内皮细胞。