Neurovascular responses to mental stress in prehypertensive humans

Neurovascular responses to mental stress have been linked to several cardiovascular diseases, including hypertension. Mean arterial pressure (MAP), muscle sympathetic nerve activity (MSNA), and forearm vascular responses to mental stress are well documented in normotensive (NT) subjects, but responses in prehypertensive (PHT) subjects remain unclear. We tested the hypothesis that PHT would elicit a more dramatic increase of MAP during mental stress via augmented MSNA and blunted forearm vascular conductance (FVC). We examined 17 PHT (systolic 120-139 and/or diastolic 80-89 mmHg; 22 ± 1 yr) and 18 NT (systolic < 120 and diastolic < 80 mmHg; 23 ± 2 yr) subjects. Heart rate, MAP, MSNA, FVC, and calf vascular conductance were measured during 5 min of baseline and 5 min of mental stress (mental arithmetic). Mental stress increased MAP and FVC in both groups, but the increases in MAP were augmented (Δ 10 ± 1 vs. Δ14 ± 1 mmHg; P < 0.05), and the increases in FVC were blunted (Δ95 ± 14 vs. Δ37 ± 8%; P < 0.001) in PHT subjects. Mental stress elicited similar increases in MSNA (Δ7 ± 2 vs. Δ6 ± 2 bursts/min), heart rate (Δ21 ± 3 vs. Δ18 ± 3 beats/min), and calf vascular conductance (Δ29 ± 10 vs. Δ19 ± 5%) in NT and PHT subjects, respectively. In conclusion, mental stress elicits an augmented pressor response in PHT subjects. This augmentation appears to be associated with altered forearm vascular, but not MSNA, responses to mental stress.     

Combined heat and mental stress alters neurovascular control in humans

This study examined the effect of combined heat and mental stress on neurovascular control. We hypothesized that muscle sympathetic nerve activity (MSNA) and forearm vascular responses to mental stress would be augmented during heat stress. Thirteen subjects performed 5 min of mental stress during normothermia (Tcore; 37 ± 0°C) and heat stress (38 ± 0°C). Heart rate, mean arterial pressure (MAP), MSNA, forearm vascular conductance (FVC; venous occlusion plethysmography), and forearm skin vascular conductance (SkVCf; via laser-Doppler) were analyzed. Heat stress increased heart rate, MSNA, SkVCf, and FVC at rest but did not change MAP. Mental stress increased MSNA and MAP during both thermal conditions; however, the increase in MAP during heat stress was blunted, whereas the increase in MSNA was accentuated, compared with normothermia (time × condition; P < 0.05 for both). Mental stress decreased SkVCf during heat stress but not during normothermia (time × condition, P < 0.01). Mental stress elicited similar increases in heart rate and FVC during both conditions. In one subject combined heat and mental stress induced presyncope coupled with atypical blood pressure and cutaneous vascular responses. In conclusion, these findings indicate that mental stress elicits a blunted increase of MAP during heat stress, despite greater increases in total MSNA and cutaneous vasoconstriction. The neurovascular responses to combined heat and mental stress may be clinically relevant to individuals frequently exposed to mentally demanding tasks in hyperthermic environmental conditions (i.e., soldiers, firefighters, and athletes).     

Phenylephrine-induced elevations in arterial blood pressure are attenuated in heat-stressed humans

To test the hypothesis that phenylephrine-induced elevations in blood pressure are attenuated in heat-stressed humans, blood pressure was elevated via steady-state infusion of three doses of phenylephrine HCl in 10 healthy subjects in both normothermic and heat stress conditions. Whole body heating significantly increased sublingual temperature by ~0.5 degrees C, muscle sympathetic nerve activity (MSNA), heart rate, and cardiac output and decreased total peripheral vascular resistance (TPR; all P < 0.005) but did not change mean arterial blood pressure (MAP; P > 0.05). At the highest dose of phenylephrine, the increase in MAP and TPR from predrug baselines was significantly attenuated during the heat stress [DeltaMAP 8.4 +/- 1.2 mmHg; DeltaTPR 0.96 +/- 0.85 peripheral resistance units (PRU)] compared with normothermia (DeltaMAP 15.4 +/- 1.4 mmHg, DeltaTPR 7.13 +/- 1.18 PRU; all P < 0.001). The sensitivity of baroreflex control of MSNA and heart rate, expressed as the slope of the relationship between MSNA and diastolic blood pressure, as well as the slope of the relationship between heart rate and systolic blood pressure, respectively, was similar between thermal conditions (each P > 0.05). These data suggest that phenylephrine-induced elevations in MAP are attenuated in heat-stressed humans without affecting baroreflex control of MSNA or heart rate.     

Vestibulosympathetic reflex during mental stress.

Increases in sympathetic neural activity occur independently with either vestibular or mental stimulation, but it is unknown whether sympathetic activation is additive or inhibitive when both stressors are combined. The purpose of the present study was to investigate the combined effects of vestibular and mental stimulation on sympathetic neural activation and arterial pressure in humans. Muscle sympathetic nerve activity (MSNA), arterial pressure, and heart rate were recorded in 10 healthy volunteers in the prone position during 1) head-down rotation (HDR), 2) mental stress (MS; using arithmetic), and 3) combined HDR and MS. HDR significantly (P < 0.05) increased MSNA (9 +/- 2 to 13 +/- 2 bursts/min). MS significantly increased MSNA (8 +/- 2 to 13 +/- 2 bursts/min) and mean arterial pressure (87 +/- 2 to 101 +/- 2 mmHg). Combined HDR and MS significantly increased MSNA (9 +/- 1 to 16 +/- 2 bursts/min) and mean arterial pressure (89 +/- 2 to 100 +/- 3 mmHg). Increases in MSNA (7 +/- 1 bursts/min) during the combination trial were not different from the algebraic sum of each trial performed alone (8 +/- 2 bursts/min). We conclude that the interaction for MSNA and arterial pressure is additive during combined vestibular and mental stimulation. Therefore, vestibular- and stress-mediated increases of MSNA appear to occur independently in humans.     

Vestibulosympathetic reflex during orthostatic challenge in aging humans

Aging attenuates the increase in muscle sympathetic nerve activity (MSNA) and elicits hypotension during otolith organ engagement in humans. The purpose of the present study was to determine the neural and cardiovascular responses to otolithic engagement during orthostatic stress in older adults. We hypothesized that age-related impairments in the vestibulosympathetic reflex would persist during orthostatic challenge in older subjects and might compromise arterial blood pressure regulation. MSNA, arterial blood pressure, and heart rate responses to head-down rotation (HDR) performed with and without lower body negative pressure (LBNP) in prone subjects were measured. Ten young (27 +/- 1 yr) and 11 older subjects (64 +/- 1 yr) were studied prospectively. HDR performed alone elicited an attenuated increase in MSNA in older subjects (Delta106 +/- 28 vs. Delta20 +/- 7% for young and older subjects). HDR performed during simultaneous orthostatic stress increased total MSNA further in young (Delta53 +/- 15%; P < 0.05) but not older subjects (Delta-5 +/- 4%). Older subjects demonstrated consistent significant hypotension during HDR performed both alone (Delta-6 +/- 2 mmHg) and during LBNP (Delta-7 +/- 2 mmHg). These data provide experimental support for the concept that age-related impairments in the vestibulosympathetic reflex persist during orthostatic challenge in older adults. Furthermore, these findings are consistent with the concept that age-related alterations in vestibular function might contribute to altered orthostatic blood pressure regulation with age in humans.     

Muscle sympathetic nerve activity during lower body negative pressure is accentuated in heat-stressed humans.

The purpose of this project was to test the hypothesis that increases in muscle sympathetic nerve activity (MSNA) during an orthostatic challenge is attenuated in heat-stressed individuals. To accomplish this objective, MSNA was measured during graded lower body negative pressure (LBNP) in nine subjects under normothermic and heat-stressed conditions. Progressive LBNP was applied at -3, -6, -9, -12, -15, -18, -21, and -40 mmHg for 2 min per stage. Whole body heating caused significant increases in sublingual temperature, skin blood flow, sweat rate, heart rate, and MSNA (all P < 0.05) but not in mean arterial blood pressure (P > 0.05). Progressive LBNP induced significant increases in MSNA in both thermal conditions. However, during the heat stress trial, increases in MSNA at LBNP levels higher than -9 mmHg were greater compared with during the same LBNP levels in normothermia (all P < 0.05). These data suggest that the increase in MSNA to orthostatic stress is not attenuated but rather accentuated in heat-stressed humans.     

Effects of lower body negative pressure on sympathetic discharge to leg muscles in humans

Recent studies indicate that nonhypotensive orthostatic stress in humans causes reflex vasoconstriction in the forearm but not in the calf. We used microelectrode recordings of muscle sympathetic nerve activity (MSNA) from the peroneal nerve in conscious humans to determine if unloading of cardiac baroreceptors during nonhypotensive lower body negative pressure (LBNP) increases sympathetic discharge to the leg muscles. LBNP from -5 to -15 mmHg had no effect on arterial pressure or heart rate but caused graded decreases in central venous pressure and corresponding large increases in peroneal MSNA. Total MSNA (burst frequency X mean burst amplitude) increased by 61 +/- 22% (P less than 0.05 vs. control) during LBNP at only -5 mmHg and rose progressively to a value that was 149 +/- 29% greater than control during LBNP at -15 mmHg (P less than 0.05). The major new conclusion is that nonhypotensive LBNP is a potent stimulus to muscle sympathetic outflow in the leg as well as the arm. During orthostatic stress in humans, the cardiac baroreflex appears to trigger a mass sympathetic discharge to the skeletal muscles in all of the extremities.     

Influence of increased central venous pressure on baroreflex control of sympathetic activity in humans

Volume expansion often ameliorates symptoms of orthostatic intolerance; however, the influence of this increased volume on integrated baroreflex control of vascular sympathetic activity is unknown. We tested whether acute increases in central venous pressure (CVP) diminished subsequent responsiveness of muscle sympathetic nerve activity (MSNA) to rapid changes in arterial pressure. We studied healthy humans under three separate conditions: control, acute 10 degrees head-down tilt (HDT), and saline infusion (SAL). In each condition, heart rate, arterial pressure, CVP, and peroneal MSNA were measured during 5 min of rest and then during rapid changes in arterial pressure induced by sequential boluses of nitroprusside and phenylephrine (modified Oxford technique). Sensitivities of integrated baroreflex control of MSNA and heart rate were assessed as the slopes of the linear portions of the MSNA-diastolic blood pressure and R-R interval-systolic pressure relations, respectively. CVP increased approximately 2 mmHg in both SAL and HDT conditions. Resting heart rate and mean arterial pressure were not different among trials. Sensitivity of baroreflex control of MSNA was decreased in both SAL and HDT condition, respectively: -3.1 +/- 0.6 and -3.3 +/- 1.0 versus -5.0 +/- 0.6 units.beat(-1).mmHg(-1) (P < 0.05 for SAL and HDT vs. control). Sensitivity of baroreflex control of the heart was not different among conditions. Our results indicate that small increases in CVP decrease the sensitivity of integrated baroreflex control of sympathetic nerve activity in healthy humans.     

Hyperoxia enhances metaboreflex sensitivity during static exercise in humans

Peripheral chemoreflex inhibition with hyperoxia decreases sympathetic nerve traffic to muscle circulation [muscle sympathetic nerve activity (MSNA)]. Hyperoxia also decreases lactate production during exercise. However, hyperoxia markedly increases the activation of sensory endings in skeletal muscle in animal studies. We tested the hypothesis that hyperoxia increases the MSNA and mean blood pressure (MBP) responses to isometric exercise. The effects of breathing 21% and 100% oxygen at rest and during isometric handgrip at 30% of maximal voluntary contraction on MSNA, heart rate (HR), MBP, blood lactate (BL), and arterial O2 saturation (SaO2) were determined in 12 healthy men. The isometric handgrips were followed by 3 min of postexercise circulatory arrest (PE-CA) to allow metaboreflex activation in the absence of other reflex mechanisms. Hyperoxia lowered resting MSNA, HR, MBP, and BL but increased Sa(O2) compared with normoxia (all P < 0.05). MSNA and MBP increased more when exercise was performed in hyperoxia than in normoxia (MSNA: hyperoxic exercise, 255 +/- 100% vs. normoxic exercise, 211 +/- 80%, P = 0.04; and MBP: hyperoxic exercise, 33 +/- 9 mmHg vs. normoxic exercise, 26 +/- 10 mmHg, P = 0.03). During PE-CA, MSNA and MBP remained elevated (both P < 0.05) and to a larger extent during hyperoxia than normoxia (P < 0.05). Hyperoxia enhances the sympathetic and blood pressure (BP) reactivity to metaboreflex activation. This is due to an increase in metaboreflex sensitivity by hyperoxia that overrules the sympathoinhibitory and BP lowering effects of chemoreflex inhibition. This occurs despite a reduced lactic acid production.     

Neurovascular responses to mental stress in the supine and upright postures.

The purpose of this study was to determine neurovascular responses to mental stress (MS) in the supine and upright postures. MS was elicited in 23 subjects (26 +/- 1 yr) by 5 min of mental arithmetic. In study 1 (n = 9), Doppler ultrasound was used to measure mean blood flow velocity in the renal (RBFV) and superior mesenteric arteries (SMBFV), and venous occlusion plethysmography was used to measure forearm blood flow (FBF). In study 2 (n = 14), leg blood flow (LBF; n = 9) was measured by Doppler ultrasound, and muscle sympathetic nerve activity (MSNA; n = 5) was measured by microneurography. At rest, upright posture increased heart rate and MSNA and decreased LBF, FBF, RBFV, and SMBFV and their respective conductances. MS elicited similar increases in mean arterial blood pressure ( approximately 12 mmHg) and heart rate ( approximately 17 beats/min), regardless of posture. MS in both postures elicited a decrease in RBFV, SMBFV, and their conductances and an increase in LBF, FBF, and their conductances. Changes in blood flow were blunted in the upright posture in all vascular beds examined, but the pattern of the vascular response was the same as the supine posture. MS did not change MSNA in either posture (change: approximately 1 +/- 3 and approximately 3 +/- 3 bursts/min, respectively). In conclusion, the augmented sympathetic activity of the upright posture does not alter heart rate, mean arterial blood pressure, or MSNA responses to MS. MS elicits divergent vascular responses in the visceral and peripheral vasculature. These results indicate that, although the upright posture attenuates vascular responses to MS, the pattern of neurovascular responses does not differ between postures.     

Baroreflex control of muscle sympathetic nerve activity during skin surface cooling.

Skin surface cooling improves orthostatic tolerance through a yet to be identified mechanism. One possibility is that skin surface cooling increases the gain of baroreflex control of efferent responses contributing to the maintenance of blood pressure. To test this hypothesis, muscle sympathetic nerve activity (MSNA), arterial blood pressure, and heart rate were recorded in nine healthy subjects during both normothermic and skin surface cooling conditions, while baroreflex control of MSNA and heart rate were assessed during rapid pharmacologically induced changes in arterial blood pressure. Skin surface cooling decreased mean skin temperature (34.9 +/- 0.2 to 29.8 +/- 0.6 degrees C; P < 0.001) and increased mean arterial blood pressure (85 +/- 2 to 93 +/- 3 mmHg; P < 0.001) without changing MSNA (P = 0.47) or heart rate (P = 0.21). The slope of the relationship between MSNA and diastolic blood pressure during skin surface cooling (-3.54 +/- 0.29 units.beat(-1).mmHg(-1)) was not significantly different from normothermic conditions (-2.94 +/- 0.21 units.beat(-1).mmHg(-1); P = 0.19). The slope depicting baroreflex control of heart rate was also not altered by skin surface cooling. However, skin surface cooling shifted the "operating point" of both baroreflex curves to high arterial blood pressures (i.e., rightward shift). Resetting baroreflex curves to higher pressure might contribute to the elevations in orthostatic tolerance associated with skin surface cooling.     

Differential effects of hydrocortisone on sympathetic and hemodynamic responses to sympathoexcitatory manoeuvres in men

Aim of the present study was to investigate the influence of hydrocortisone on muscle sympathetic nerve activity (MSNA) and hemodynamic parameters during different sympathoexcitatory manoeuvres in humans. The study focuses on the interaction of the hypothalamo-pituitary-adrenal system and the sympathetic nervous system. Hydrocortisone 100 mg or placebo was administered intravenously to eight young healthy subjects in a double-blind crossover design. After 6 h, blood pressure, heart rate and MSNA from the peroneal nerve were recorded at rest, during an arithmetic stress task, an apnea and a cold pressor test. Hydrocortisone treatment increased serum cortisol levels to the upper physiological range and suppressed basal levels of adrenocorticotropin. During mental stress, MSNA, heart rate and blood pressure levels were elevated independently of hydrocortisone pre-treatment. However, hydrocortisone induced a sustained increase in basal heart rate throughout the whole experiment. A stronger increase in diastolic blood pressure was observed during apnea and cold pressor test in the hydrocortisone experiments. MSNA or plasma catecholamines at rest or during the manoeuvres were not affected by hydrocortisone. The observed hydrocortisone effects may be due to an increased responsiveness of adrenergic receptors towards catecholamines or a central modulation of the baroreflex involving parasympathetic mechanisms. Further studies are needed to confirm that the increase in MSNA during mental stress does not depend on a concomitant activation of the hypothalamo-pituitary-adrenal system.     

Sympathetic vascular transduction is augmented in young normotensive blacks.

The purpose of the present study was to determine sympathetic vascular transduction in young normotensive black and white adults. We hypothesized that blacks would demonstrate augmented transduction of muscle sympathetic nerve activity (MSNA) into vascular resistance. To test this hypothesis, MSNA, forearm blood flow, heart rate, and arterial blood pressure were measured during lower body negative pressure (LBNP). At rest, no differences existed in arterial blood pressure, heart rate, forearm blood flow, and forearm vascular resistance (FVR). Likewise, LBNP elicited comparable responses of these variables for blacks and whites. Baseline MSNA did not differ between blacks and whites, but whites demonstrated greater increases during LBNP (28 +/- 7 vs. 55 +/- 18%, 81 +/- 21 vs. 137 +/- 42%, 174 +/- 81 vs. 556 +/- 98% for -5, -15, and -40 mmHg LBNP, respectively; P < 0.001). Consistent with smaller increases in MSNA but similar FVR responses during LBNP, blacks demonstrated greater sympathetic vascular transduction (%FVR/%MSNA) than whites (0.95 +/- 0.07 vs. 0.82 +/- 0.07 U; 0.82 +/- 0.11 vs. 0.64 +/- 0.09 U; 0.95 +/- 0.37 vs. 0.35 +/- 0.09 U; P < 0.01). In summary, young whites demonstrate greater increases in MSNA during baroreceptor unloading than age-matched normotensive blacks. However, more importantly, for a given increase in MSNA, blacks demonstrate greater forearm vasoconstriction than whites. This finding may contribute to augmented blood pressure reactivity in blacks.     

Hypoxia potentiates exercise-induced sympathetic neural activation in humans.

Our purpose was to test the hypothesis that hypoxia potentiates exercise-induced sympathetic neural activation in humans. In 15 young (20-30 yr) healthy subjects, lower leg muscle sympathetic nerve activity (MSNA, peroneal nerve; microneurography), venous plasma norepinephrine (PNE) concentrations, heart rate, and arterial blood pressure were measured at rest and in response to rhythmic handgrip exercise performed during normoxia or isocapnic hypoxia (inspired O2 concn of 10%). Study I (n = 7): Brief (3-4 min) hypoxia at rest did not alter MSNA, PNE, or arterial pressure but did induce tachycardia [17 +/- 3 (SE) beats/min; P less than 0.05]. During exercise at 50% of maximum, the increases in MSNA (346 +/- 81 vs. 207 +/- 14% of control), PNE (175 +/- 25 vs. 120 +/- 11% of control), and heart rate (36 +/- 2 vs. 20 +/- 2 beats/min) were greater during hypoxia than during normoxia (P less than 0.05), whereas the arterial pressure response was not different (26 +/- 4 vs. 25 +/- 4 mmHg). The increase in MSNA during hypoxic exercise also was greater than the simple sum of the separate responses to hypoxia and normoxic exercise (P less than 0.05). Study II (n = 8): In contrast to study I, during 2 min of exercise (30% max) performed under conditions of circulatory arrest and 2 min of postexercise circulatory arrest (local ischemia), the MSNA and PNE responses were similar during systemic hypoxia and normoxia. Arm ischemia without exercise had no influence on any variable during hypoxia or normoxia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of lower body positive pressure on muscle sympathetic nerve activity response to head-up tilt

The present study was performed to test the hypothesis that application of lower body positive pressure (LBPP) during orthostasis would reduce the baroreflex-mediated enhancement in sympathetic activity in humans. Eight healthy young men were exposed to a 70 degrees head-up tilt (HUT) on application of 30 mmHg LBPP. Muscle sympathetic nerve activity (MSNA) was microneurographically recorded from the tibial nerve, along with hemodynamic variables. We found that in the supine position with LBPP, MSNA remained unchanged (13.4 +/- 3.3 vs. 11.8 +/- 2.3 bursts/min, without vs. with LBPP; P > 0.05), mean arterial pressure was elevated, but arterial pulse pressure and heart rate did not alter. At 70 degrees HUT with LBPP, the enhanced MSNA response was reduced (33.8 +/- 5.0 vs. 22.5 +/- 2.2 bursts/min, without vs. with LBPP; P < 0.05), mean arterial pressure was higher, the decreased pulse pressure was restored, and the increased heart rate was attenuated. We conclude that the baroreflex-mediated enhancement in sympathetic activity during HUT was reduced by LBPP. Application of LBPP in HUT induced an obvious cephalad fluid shift as well as a restoration of arterial pulse pressure, which reduced the inhibition of the baroreceptors. However, the activation of the intramuscular mechanoreflexes produced by 30 mmHg LBPP might counteract the effects of baroreflexes.     

Modulation of control of muscle sympathetic nerve activity during orthostatic stress in humans

We tested the hypothesis that orthostatic stress would modulate the arterial baroreflex (ABR)-mediated beat-by-beat control of muscle sympathetic nerve activity (MSNA) in humans. In 12 healthy subjects, ABR control of MSNA (burst incidence, burst strength, and total activity) was evaluated by analysis of the relation between beat-by-beat spontaneous variations in diastolic blood pressure (DAP) and MSNA during supine rest (CON) and at two levels of lower body negative pressure (LBNP: -15 and -35 mmHg). At -15 mmHg LBNP, the relation between burst incidence (bursts per 100 heartbeats) and DAP showed an upward shift from that observed during CON, but the further shift seen at -35 mmHg LBNP was only marginal. The relation between burst strength and DAP was shifted upward at -15 mmHg LBNP (vs. CON) and further shifted upward at -35 mmHg LBNP. At -15 mmHg LBNP, the relation between total activity and DAP was shifted upward from that obtained during CON and further shifted upward at -35 mmHg LBNP. These results suggest that ABR control of MSNA is modulated during orthostatic stress and that the modulation is different between a mild (nonhypotensive) and a moderate (hypotensive) level of orthostatic stress.     

Hypoxia augments apnea-induced peripheral vasoconstriction in humans.

Obstructive apnea and voluntary breath holding are associated with transient increases in muscle sympathetic nerve activity (MSNA) and arterial pressure. The contribution of changes in blood flow relative to the contribution of changes in vascular resistance to the apnea-induced transient rise in arterial pressure is unclear. We measured heart rate, mean arterial blood pressure (MAP), MSNA (peroneal microneurography), and femoral artery blood velocity (V(FA), Doppler) in humans during voluntary end-expiratory apnea while they were exposed to room air, hypoxia (10.5% inspiratory fraction of O2), and hyperoxia (100% inspiratory fraction of O2). Changes from baseline of leg blood flow (Q) and vascular resistance (R) were estimated from the following relationships: Q proportional to V(FA), corrected for the heart rate, and R proportional to MAP/Q. During apnea, MSNA rose; this rise in MSNA was followed by a rise in MAP, which peaked a few seconds after resumption of breathing. Responses of MSNA and MAP to apnea were greatest during hypoxia and smallest during hyperoxia (P < 0.05 for both compared with room air breathing). Similarly, apnea was associated with a decrease in Q and an increase in R. The decrease in Q was greatest during hypoxia and smallest during hyperoxia (-25 +/- 3 vs. -6 +/- 4%, P < 0.05), and the increase in R was the greatest during hypoxia and the least during hyperoxia (60 +/- 8 vs. 21 +/- 6%, P < 0.05). Thus voluntary apnea is associated with vasoconstriction, which is in part mediated by the sympathetic nervous system. Because apnea-induced vasoconstriction is most intense during hypoxia and attenuated during hyperoxia, it appears to depend at least in part on stimulation of arterial chemoreceptors.     

Baroreflex modulation of muscle sympathetic nerve activity during cold pressor test in humans

The purpose of this project was to test the hypothesis that baroreceptor modulation of muscle sympathetic nerve activity (MSNA) and heart rate is altered during the cold pressor test. Ten subjects were exposed to a cold pressor test by immersing a hand in ice water for 3 min while arterial blood pressure, heart rate, and MSNA were recorded. During the second and third minute of the cold pressor test, blood pressure was lowered and then raised by intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure was more negative (P < 0.005) during the cold pressor test (-244.9 +/- 26.3 units x beat(-1) x mmHg(-1)) when compared with control conditions (-138.8 +/- 18.6 units x beat(-1) x mmHg(-1)), whereas no significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. These data suggest that baroreceptors remain capable of modulating MSNA and heart rate during a cold pressor test; however, the sensitivity of baroreflex modulation of MSNA is elevated without altering the sensitivity of baroreflex control of heart rate.     

Interactions of plasma osmolality with arterial and central venous pressures in control of sympathetic activity and heart rate in humans

Plasma osmolality alters control of sympathetic activity and heart rate in animal models; however, it is unknown whether physiological increases in plasma osmolality have such influences in humans and what effect concurrent changes in central venous and/or arterial pressures may have. We tested whether physiological increases in plasma osmolality (similar to those during exercise dehydration) alter control of muscle sympathetic nerve activity (MSNA) and heart rate (HR) in humans. We studied 17 healthy young adults (7 women, 10 men) at baseline and during arterial pressure (AP) transients induced by sequential injections of nitroprusside and phenylephrine, under three conditions: control (C), after 1 ml/kg intravenous hypertonic saline (HT1), and after 2 ml/kg hypertonic saline (HT2). We continuously measured HR, AP, central venous pressure (CVP; peripherally inserted central catheter) and MSNA (peroneal microneurography) in all conditions. Plasma osmolality increased from 287 +/- 1 mosmol/kg in C to 290 +/- 1 mosmol/kg in HT1 (P < 0.05) but did not increase further in HT2 (291 +/- 1 mosmol/kg; P > 0.05 vs. C). Mean AP and CVP were similar between C and HT1, but both increased slightly in HT2. HR increased slightly but significantly during both HT1 and HT2 vs. C (P < 0.05). Sensitivity of baroreflex control of MSNA was significantly increased vs. C in HT1 [-7.59 +/- 0.97 (HT1) vs. -5.85 +/- 0.63 (C) arbitrary units (au).beat(-1).mmHg(-1); P < 0.01] but was not different in HT2 (-6.55 +/- 0.94 au.beat(-1).mmHg(-1)). We conclude that physiological changes in plasma osmolality significantly alter control of MSNA and HR in humans, and that this influence can be modified by CVP and AP.     

Forebrain regions associated with postexercise differences in autonomic and cardiovascular function during baroreceptor unloading

The cortical regions representing peripheral autonomic reactions in humans are poorly understood. This study examined whether changes in forebrain activity were associated with the altered physiological responses to lower body negative pressure (LBNP) following a single bout of dynamic exercise (POST-EX). We hypothesized that, compared with the nonexercised condition (NO-EX), POST-EX would elicit greater reductions in stroke volume (SV) and larger increases in heart rate (HR) and muscle sympathetic nerve activity (MSNA) during LBNP (5, 15, and 35 mmHg). Forebrain neural activity (n = 11) was measured using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. HR, SV, arterial blood pressure (ABP), and MSNA were collected separately. Compared with NO-EX, baseline ABP was reduced, whereas HR and total vascular conductance (TVC) were elevated in POST-EX (P < 0.05). In both conditions, 5 mmHg LBNP did not elicit a change (from baseline) in any physiological parameter. Compared with NO-EX, 35 mmHg LBNP-mediated decreases in SV and TVC produced greater increases in HR and MSNA during POST-EX (P < 0.05). The right posterior insula and dorsal anterior cingulate cortex demonstrated a larger decrease in BOLD at 5 mmHg LBNP but greater BOLD increase at 15 and 35 mmHg LBNP POST-EX vs. NO-EX (P < 0.005). Conversely, the thalamus and ventral medial prefrontal cortex displayed the opposite BOLD activity pattern (i.e., larger increase at 5 mmHg LBNP but greater decrease at 15 and 35 mmHg LBNP POST-EX vs. NO-EX). Our findings suggest that discrete forebrain regions may be involved with the generation of baroreflex-mediated sympathetic and cardiovascular responses elicited by moderate LBNP.