Effect of baroreflex loading on the responsiveness of the vestibulosympathetic reflex in humans.

Activation of the vestibular otolith organs with head-down rotation (HDR) increases muscle sympathetic nerve activity (MSNA) in humans. Previously, we demonstrated this vestibulosympathetic reflex (VSR) elicits increases in MSNA during baroreflex unloading (i.e., lower body negative pressure) in humans. Whether such an effect persists during baroreflex loading is unknown. We tested the hypothesis that the ability of the VSR to increase MSNA is preserved during baroreflex unloading and inhibited during baroreflex loading. Ten subjects (26 +/- 1 yr) performed three trials of HDR to activate the VSR. These trials were performed after a period of sustained saline (control), nitroprusside (baroreflex unloading: 0.8-1.0 microg.kg(-1).min(-1)), and phenylephrine (baroreflex loading: 0.6-0.8 microg.kg(-1).min(-1)) infusion. Nitroprusside infusion decreased (Delta7 +/- 1 mmHg, where Delta is change; P < 0.001) and phenylephrine infusion increased mean arterial pressure (Delta8 +/- 1 mmHg; P < 0.001) at rest. HDR performed during the control [Delta3 +/- 2 bursts/min, Delta314 +/- 154 arbitrary units (au) total activity, Delta41 +/- 18% total activity; P < 0.05] and nitroprusside trials [Delta5 +/- 2 bursts/min, Delta713 +/- 241 au total activity, Delta49 +/- 20% total activity; P < 0.05] increased MSNA similarly despite significantly elevated levels at rest (13 +/- 2 to 26 +/- 3 bursts/min) in the latter. In contrast, HDR performed during the phenylephrine trial failed to increase MSNA (Delta0 +/- 1 bursts/min, Delta-15 +/- 33 au total activity, Delta-8 +/- 21% total activity). These results confirm previous findings that the ability of the VSR to increase MSNA is preserved during baroreflex unloading. In contrast, the ability of the VSR to increase MSNA is abolished during baroreflex loading. These results provide further support for the concept that the VSR may act primarily to defend against hypotension in humans.     

Greater sensitivity of the vestibulosympathetic reflex in the upright posture in humans.

Otolith organs have been shown to activate the sympathetic nervous system in the prone position by head-down rotation (HDR) in humans. To date, otolithic stimulation by HDR has not been comprehensively studied in the upright posture. The purpose of the present study was to determine whether otolithic stimulation increases muscle sympathetic nerve activity (MSNA) in the upright posture. It was hypothesized that stimulation of the otolith organs would increase MSNA in the upright posture, despite increased baseline sympathetic activation due to unloading of the baroreceptors. MSNA, arterial blood pressure, heart rate, and degree of head rotation were measured during HDR in 18 volunteers (23 +/- 1 yr) in different postures. Study 1 (n = 11) examined HDR in the prone and sitting positions and study 2 (n = 7) examined HDR in the prone and 60 degrees head-up tilt positions. Baseline MSNA was 8 +/- 4, 15 +/- 4, and 33 +/- 2 bursts/min for prone, sitting, and head-up tilt, respectively. HDR significantly increased MSNA in the prone (Delta4 +/- 1 and Delta105 +/- 37% for burst frequency and total activity, respectively), sitting (Delta5 +/- 1 and Delta43 +/- 12%), and head-up tilt (Delta7 +/- 1 and Delta110 +/- 41%; P < 0.05). Sensitivity of the vestibulosympathetic reflex (%DeltaMSNA/DeltaHDR; degree of head rotation) was significantly greater in the sitting and head-up tilt than prone position (prone = 74 +/- 22; sitting = 109 +/- 30; head-up tilt = 276 +/- 103; P < 0.05). These data indicate that stimulation of the otolith organs can mediate increases in MSNA in the upright posture and suggest a greater sensitivity of the vestibulosympathetic reflex in the upright posture in humans.     

Glycerol-induced fluid shifts attenuate the vestibulosympathetic reflex in humans

The glycerol dehydration test (GDT) has been used to test for the presence of Ménière's disease and elicits acute alterations in vestibular reflexes in both normal and pathological states. Activation of the vestibulosympathetic reflex (VSR) increases muscle sympathetic nerve activity (MSNA) and peripheral vascular resistance. We hypothesized that the GDT would attenuate the VSR through fluid shifts of the inner ear. Sixteen male subjects (26 ± 1 yr) were randomly assigned to be administered either glycerol mixed with cranberry juice (97 ± 3 ml glycerol + equal portion of cranberry juice; n = 9) or a placebo control [water + cranberry juice (100 ml each); n = 7]. Subjects in both groups performed head-down rotation (HDR), which engages the VSR, before and after administration of either the glycerol or placebo. MSNA (microneurography), arterial blood pressure, and leg blood flow (venous occlusion plethysmography) were measured during HDR. Before glycerol administration, HDR significantly increased MSNA burst frequency (Δ8 ± 1 bursts/min; P < 0.01) and total activity (Δ77 ± 18%; P < 0.01) and decreased calf vascular conductance (-Δ20 ± 3%; P < 0.01). However, HDR performed postadministration of glycerol resulted in an attenuated MSNA increase (Δ3 ± 1 bursts/min, Δ22 ± 3% total activity) and decrease in calf vascular conductance (-Δ7 ± 4%). HDR significantly increased MSNA burst frequency (Δ5 ± 1 and Δ5 ± 2 bursts/min) and total activity (Δ58 ± 13% and Δ52 ± 18%) in the placebo group before and after placebo, respectively (P < 0.01). Likewise, decreases in calf vascular conductance during HDR before and after placebo were not different (-Δ13 ± 4% and -Δ14 ± 2%, respectively; P < 0.01). These results suggest that fluid shifts of the inner ear via glycerol dehydration attenuate the VSR. These data provide support that inner ear fluid dynamics can have a significant impact on blood pressure regulation via the VSR in humans.     

Aging, opioid-receptor agonists and antagonists, and the vestibulosympathetic reflex in humans.

Animal studies indicate that opioids inhibit the firing rate of vestibular neurons, which are important in mediating the vestibulosympathetic reflex. Furthermore, this inhibition appears to be greater in more mature rats. In the present study, we tested the hypotheses that opioids inhibit the vestibulosympathetic reflex in humans and that endogenous opioids contribute to the age-related impairment of the vestibulosympathetic reflex. These hypotheses were tested by measuring muscle sympathetic nerve activity (MSNA), arterial blood pressure, and heart rate responses to otolith organ engagement during head-down rotation (HDR) in young (24 +/- 2 yr old) and older (63 +/- 2 yr) subjects before and after administration of either an opioid-receptor antagonist (16 mg naloxone in 9 young and 8 older subjects) or an opioid-receptor agonist (60 mg codeine in 7 young and 7 older subjects). Naloxone did not augment the reflex increase in MSNA during HDR in young (Delta7 +/- 2 vs. Delta4 +/- 2 bursts/min and Delta81 +/- 23 vs. Delta60 +/- 24% change in burst frequency and total MSNA before and after naloxone, respectively) or older subjects (Delta2 +/- 2 vs. Delta1 +/- 2 burst/min and Delta8 +/- 7 vs. Delta8 +/- 9% before and after naloxone). Similarly, codeine did not attenuate the increase in MSNA during HDR in young (Delta8 +/- 1 vs. Delta7 +/- 2 bursts/min and Delta53 +/- 4 vs. Delta64 +/- 16% before and after codeine) or older subjects (Delta6 +/- 4 vs. Delta3 +/- 3 bursts/min and Delta38 +/- 21 vs. Delta33 +/- 20%). Mean arterial blood pressure and heart rate responses to HDR were not altered by either naloxone or codeine. These data do not provide experimental support for the concept that opioids modulate the vestibulosympathetic reflex in humans. Moreover, endogenous opioids do not appear to contribute the age-associated impairment of the vestibulosympathetic reflex.     

Effect of exercise and thermal stress on plasma volume.

Six male subjects exercised for 50 min at 25% (light exercise) and 55% (moderate exercise) of their estimated aerobic capacities in environments of 42 degrees C db, 35 degrees C wb and 30 degrees C db, 24 degrees C wb, respectively. Alterations in the hematocrit, hemoglobin, and plasma protein concentrations, and in the activity of an injected aliquot of isotopically labeled albumin were each used to calculate the percentage change in plasma volume occurring during exercise and recovery. Changes in each measure were consistent with a reduction in plasma volume during exercise and a return to preexercise levels during recovery. There was no significant difference between the measures when exercising in the heat, but during the more severe exercise in the cooler environment disproportional changes in protein, hematocrit, and hemoglobin were observed. Disproportional changes were also seen during the recovery phase, when the hematocrit and hemoglobin concentration indicated a more rapid return of the plasma volume to preexercise levels than did either the plasma protein concentration or albumin activity. During moderate exercise and recovery there was a 1% decrease in red cell volume. It is concluded that exercise accelerates the rate of protein movement from extravascular compartments to the intravascular compartment, leading to elevated plasma protein levels during recovery which favor the return of water to the intravascular space. Hemoglobin concentration is considered to be the most reliable measure of plasma volume change during exercise.     

Effect of transrespiratory pressure on PETCO2-PaCO2 and ventilatory reflexes in humans

Inspiratory muscle activity increases when lung volume is increased by continuous positive-pressure breathing in conscious human subjects (Green et al., Respir. Physiol. 35: 283-300, 1978). Because end-tidal CO2 pressure (PETCO2) does not change, these increases have not been attributed to chemoreflexes. However, continuous positive-pressure breathing at 20 cmH2O influences the end-tidal to arterial CO2 pressure differences (Folkow and Pappenheimer, J. Appl. Physiol. 8: 102-110, 1955). We have compared PETCO2 with arterial CO2 pressure (PaCO2). We have compared PETCO2 with arterial CO2 pressure (PaCO2) in healthy human subjects exposed to continuous positive airway pressure (10 cmH2O) or continuous negative pressure around the torso (-15 cmH2O) sufficient to increase mean lung volume by about 650 ml. The difference between PETCO2 and PaCO2 was not decreased, and we conclude that PETCO2 is a valid measure of chemical drive to ventilation in such circumstances. We observed substantial increases in respiratory muscle electromyograms during pressure breathing as seen previously and conclude this response must originate by proprioception. On average, the compensation of tidal volume thus afforded was complete, but the wide variability of individual responses suggests that there was a large cerebral cortical component in the responses seen here.     

Relative role of low- and high pressure reflexes on sympathetic activity in humans during simulated gravitational stress

In order to determine the relative role of low- and high-pressure reflexes, respectively, on forearm sympathetic nerve activity (fSNA), 10 normal male subjects underwent a 4-step (5 min each) graded lower body negative pressure (LBNP) from -10 to -50 mmHg. Central venous pressure (CVP) and stroke volume gradually decreased (p<0.05), and arterial pulse pressure (PP) abruptly decreased at LBNP of -50 mmHg. Mean arterial pressure (MAP) remained unchanged. Forearm venous plasma norepinephrine concentration (fvNE) increased significantly at LBNP of -35 mmHg (p<0.05) and with a further sharp increase during LBNP of -50 mmHg (p<0.05). High degrees of intra-individual correlations were observed between changes in Log [fvNE] and CVP (r-values from -0.78 to -0.96, p<0.01). We conclude that low-pressure reflexes are the major determinants of fSNA during non-hypotensive gravitational stress (MAP and PP unchanged). When the gravitational stress is more pronounced, a decrease in PP further augments fSNA through inhibition of high-pressure arterial baroreflexes.     

Effect of thermal stress on protein expression in the mussel Mytilus galloprovincialis Lmk

The exposure of organisms to stressing agents may affect the level and pattern of protein expression. Certain proteins with an important role in protein homeostasis and in the tolerance to stress, known as stress proteins, are especially affected. Different tissues and cells show a range of sensitivities to stress, depending on the habitat to which organisms have adapted. The response of different tissues and cells from the mussel Mytilus galloprovincialis Lmk. to heat shock has been studied in this work using different exposure times and temperatures. During the assays, protein expression was observed to vary depending on the tissue studied, the temperature or the exposure time used. But maybe the most prominent thing is the different response obtained from the cultured haemocytes and those freshly obtained from stressed mussels, which makes us think that the extraction procedure is the main cause of the response of non-cultured cells, although the haemolymph may contain components that modulate haemocyte response.     

Functional asymmetry in carotid sinus cardiac reflexes in humans

The reflex cardiac response to activation (CBA) and inactivation (CBI) of the left and right carotid baroreceptors was studied in 30 healthy subjects, aged between 24 and 38 years. The CBA was evoked by applying negative pressure (from -20 to -60 mmHg) for 10 s to the left and right carotid sinus regions separately or both together, using two small neck capsules. The CBI was produced by applying left and right positive neck pressure (from 20 to 60 mmHg) for 10 s. The blood flow velocity was measured non-invasively with a Doppler scanner placed in the suprasternal notch. Blood flow acceleration was calculated and used as an indication of left cardiac contractility. Heart rate was measured continuously. Differences were found between right and left carotid sinus responses to CBA and CBI. The maximal response of the R-R interval was significantly greater during right CBA than during left CBA (the average gain: R-R.mmHg-1 2.69 ms.mmHg-1 and 1.75 ms.mmHg-1, respectively). Also, the reflex CBI response was significantly greater for the right (3.16 ms.mmHg-1) than for the left (2.22 ms.mmHg-1). The reflex decrease/increase in blood-flow acceleration in response to CBA/CBI was significantly greater during left than during right-sided activation/inactivation. It is suggested that the functional asymmetry was related to differences in right/left-sided cardiac innervation as well as to central ipsilateral projection of the carotid baroreceptor afferents to the nuclei tractus solitarii.     

Effect of uniform and non-uniform skin temperature on thermal exchanges in water in humans

We investigated the effect of uniform (UST) and non-uniform (NUST) skin temperature on thermal exchanges during a 3-h water immersion in five male subjects wearing (NUST) or not wearing (UST) a water-perfused garment. UST was achieved by immersing the nude subject in water up to the neck. For each subject, the water temperature was adjusted to the critical temperature ( T(cw), 31.4 +/- 0.9 degrees C) or 3 degrees C below T(cw) ( T(cw) - 3). NUST was achieved by perfusing different segments of the perfused garment with water of different temperatures. The water temperature of the segment was independently adjusted according to the skin temperature distribution in cold air, the mean skin temperature being the same as the UST. At T(cw) and T(cw) - 3, changes in esophageal and mean skin temperatures were identical in UST and NUST conditions, but the skin temperature of the trunk was higher and that of the limb was lower in the NUST condition. Heat production and the overall skin heat flux at T(cw) were identical in the two conditions, but those at T(cw) - 3 were about 25% lower ( P < 0.05) in NUST than in UST conditions. At T(cw) - 3, the overall tissue insulation was 36% higher ( P < 0.05) in NUST than in UST conditions, mainly because of higher limb insulation. Thermogenesis due to shivering was lower by 62% ( P < 0.05) in NUST than in UST. We conclude that the NUST condition increased tissue insulation and suppressed shivering. This suggests that a high skin temperature of the trunk attenuates shivering in cold water and increases the ability to defend body temperature more economically in cold water.     

Rectal and colonic distension elicit viscerovisceral reflexes in humans

Colonic transit is slowed in patients with disordered rectal evacuation, but the mechanism of this phenomenon is unclear. Our objective was to investigate rectocolonic inhibitory reflexes in humans to provide potential insight into patients with obstructed defecation. In 30 healthy subjects, a barostat-manometric assembly recorded colonic tone and phasic activity in the descending colon during rectal distension and recorded rectal tone during colonic distension. Phasic distensions were 8, 16, and 32 mmHg above balloon operating pressure, and staircase inflations were comprised of balloon inflation then deflation in 2-mmHg increments at 30-s intervals from 0 to 36 mmHg. Colonic balloon volumes increased to a similar extent during phasic rectal distensions 8, 16, and 32 mmHg above operating pressure, reflecting reduced colonic tone; balloon volumes also increased and phasic pressure activity decreased during staircase rectal distensions. In contrast, rectal balloon volume declined, reflecting increased tone during phasic and staircase colonic distensions. Thus rectal distension inhibited colonic motor activity, indicative of a viscerovisceral inhibitory reflex.