Paraventricular nucleus bicuculline alters frequency components of sympathetic nerve discharge bursts

Autospectral and coherence analyses were used to determine the effect of paraventricular nucleus (PVN) GABA(A) receptor antagonism [microinfusion or microinjections of bicuculline methiodide (BMI) 100 pmoles] on sympathetic nerve discharge (SND) frequency components (bursting pattern and relationships between discharges in regionally selective nerves) in alpha-chloralose-anesthetized rats. SND was recorded from the renal, splenic, and lumbar nerves. The following observations were made. First, PVN BMI microinjections, but not PVN saline or cortical BMI microinjections, transformed the cardiac-related SND bursting pattern in baroreceptor-innervated rats to one characterized by the presence of low-frequency bursts not synchronized to the cardiac cycle or phrenic nerve discharge bursts. Second, SND pattern changes were similar in the renal, splenic, and lumbar nerves, and peak coherence values relating low-frequency bursts in sympathetic nerve pairs (renal-splenic, renal-lumbar, and splenic-lumbar) were significantly increased from preinjection control after PVN BMI microinjection. Third, PVN BMI microinjections significantly increased the coupling between low-frequency SND bursts in baroreceptor-denervated rats. Finally, PVN BMI-induced changes in the SND bursting pattern were not observed after PVN pretreatment with muscimol (GABA agonist, 1 nmole). We conclude that PVN GABA(A) receptor antagonism profoundly alters the frequency components in sympathetic nerves.     

Aging alters regulation of visceral sympathetic nerve responses to acute hypothermia

Hypothermia produced by acute cooling prominently alters sympathetic nerve outflow. Skin sympathoexcitatory responses to skin cooling are attenuated in aged compared with young subjects, suggesting that advancing age influences sympathetic nerve responsiveness to hypothermia. However, regulation of skin sympathetic nerve discharge (SND) is only one component of the complex sympathetic nerve response profile to hypothermia. Whether aging alters the responsiveness of sympathetic nerves innervating other targets during acute cooling is not known. In the present study, using multifiber recordings of splenic, renal, and adrenal sympathetic nerve activity, we tested the hypothesis that hypothermia-induced changes in visceral SND would be attenuated in middle-aged and aged compared with young Fischer 344 (F344) rats. Colonic temperature (Tc) was progressively reduced from 38 degrees C to 31 degrees C in young (3 to 6 mo), middle-aged (12 mo), and aged (24 mo) baroreceptor-innervated and sinoaortic-denervated (SAD), urethane-chloralose anesthetized, F344 rats. The following observations were made. 1) Progressive hypothermia significantly (P < 0.05) reduced splenic, renal, and adrenal SND in young baroreceptor-innervated F344 rats. 2) Reductions in splenic, renal, and adrenal SND to progressive hypothermia were less consistently observed and, when observed, were generally attenuated in baroreceptor-innervated middle-aged and aged compared with young F344 rats. 3) Differences in splenic, renal, and adrenal SND responses to reduced Tc were observed in SAD young, middle-aged, and aged F344 rats, suggesting that age-associated attenuations in SND responses to acute cooling are not the result of age-dependent modifications in arterial baroreflex regulation of SND. These findings demonstrate that advancing chronological age alters the regulation of visceral SND responses to progressive hypothermia, modifications that may contribute to the inability of aged individuals to adequately respond to acute bouts of hypothermia.     

Altered frequency responses of sympathetic nerve discharge bursts after IL-1beta and mild hypothermia.

Although interleukin-1beta (IL-1beta) administration produces nonuniform changes in the level of sympathetic nerve discharge (SND), the effect of IL-1beta on the frequency-domain relationships between discharges in different sympathetic nerves is not known. Autospectral and coherence analyses were used to determine the effect of IL-1beta and mild hypothermia (60 min after IL-1beta, colonic temperature from 38 degrees C to 36 degrees C) on the relationships between renal-interscapular brown adipose tissue (IBAT) and splenic-lumbar sympathetic nerve discharges in chloralose-anesthetized rats. The following observations were made. 1) IL-1beta did not alter renal-IBAT coherence values in the 0- to 2-Hz frequency band or at the cardiac frequency (CF). 2) Peak coherence values relating splenic-lumbar discharges at the CF were significantly increased after IL-1beta and during hypothermia. 3) Hypothermia after IL-1beta significantly reduced the coupling (0-2 Hz and CF) between renal-IBAT but not splenic-lumbar SND bursts. 4) Combining IL-1beta and mild hypothermia had a greater effect on renal-IBAT SND coherence values than did mild hypothermia alone. These data demonstrate functional plasticity in sympathetic neural circuits and suggest complex relationships between immune products and SND regulation.     

Effects of midbrain and spinal cord transections on sympathetic nerve responses to heating

In the present study, we investigated the contributions of forebrain, brain stem, and spinal neural circuits to heating-induced sympathetic nerve discharge (SND) responses in chloralose-anesthetized rats. Frequency characteristics of renal and splenic SND bursts and the level of activity in these nerves were determined in midbrain-transected (superior colliculus), spinal cord-transected [first cervical vertebra (C1)], and sham-transected (midbrain and spinal cord) rats during progressive increases in colonic temperature (T(c)) from 38 to 41.6-41.7 degrees C. The following observations were made. 1) Significant increases in renal and splenic SND were observed during hyperthermia in midbrain-transected, sham midbrain-transected, C1-transected, and sham C1-transected rats. 2) Heating changed the discharge pattern of renal and splenic SND bursts and was associated with prominent coupling between renal-splenic discharge bursts in midbrain-transected, sham midbrain-transected, and sham C1-transected rats. 3) The pattern of renal and splenic SND bursts remained unchanged from posttransection recovery levels during heating in C1-transected rats. We conclude that an intact forebrain is not required for the full expression of SND responses to increased T(c) and that spinal neural systems, in the absence of supraspinal circuits, are unable to markedly alter the frequency characteristics of SND in response to acute heat stress.     

Adrenal versus nonadrenal sympathetic preganglionic neurones in the lower thoracic intermediolateral nucleus of the cat: physiological properties

Adrenal and nonadrenal sympathetic preganglionic neurones (SPNs) in the intermediolateral nucleus of spinal segments T8-T10 in the cat were compared according to a number of physiological properties. An SPN was classified as "adrenal" (n = 37) if it could be antidromically activated by electrical stimulation of the adrenal medulla. An SPN that could not be activated from the adrenal medulla yet could be antidromically activated by electrical stimulation of the greater splanchnic nerve was classified as "nonadrenal" (n = 123). Approximately 50% of adrenal SPNs (17 out of 37) were activated antidromically by stimulation of both the greater splanchnic nerve and adrenal medulla, suggesting that these neurones projected to the adrenal medulla via the greater splanchnic nerve, with the other adrenal SPNs taking a different route. The mean conduction velocities of adrenal (6.7 +/- 1.8 (SD) m/s) and nonadrenal (6.7 +/- 1.5 m/s) sympathetic preganglionic axons were similar. Over 80% of adrenal (31 out of 37) and nonadrenal (104 out of 116) SPNs were spontaneously active. The two types of neurone were indistinguishable in terms of the rates and patterns of discharge. Adrenal SPNs discharged with a mean rate of 1.4 +/- 1.1 spikes/s, and nonadrenal SPNs discharged with a mean rate of 1.8 +/- 1.4 spikes/s. With both types of SPN, the pattern of spontaneous activity was either irregular or phasic. With the latter pattern, periodic bursts of discharge were at the same frequency as oscillations in arterial pressure, frequency of ventilation, or phrenic nerve discharge. These data suggest that adrenal and nonadrenal sympathetic preganglionic neurones in the intermediolateral nucleus in caudal thoracic segments share a number of common physiological properties.     

Sympathetic nerve regulation to heating is altered in senescent rats

Renal and splanchnic sympathetic nerve discharge (SND) responses to increased (38-41 degrees C) internal temperature were determined in anesthetized young (3-6 mo old), mature (12 mo old), and senescent (24 mo old) Fischer 344 (F344) rats. We hypothesized that SND responses would be altered in senescent and mature rats as demonstrated by attenuated sympathoexcitatory responses to heating and by the absence of hyperthermia-induced SND pattern changes. The following observations were made. 1) Renal and splanchnic SND responses were significantly increased during heating in young and mature but not in senescent rats. 2) At 41 degrees C, renal and splanchnic SND responses were higher in young compared with senescent rats, and renal SND was higher in mature than in senescent rats. 3) Heating changed the SND bursting pattern in young, but not in mature or senescent, rats. 4) SND responses to heating did not differ between baroreceptor-innervated (BRI) and sinoaortic-denervated (SAD) senescent rats but were higher in SAD compared with BRI young rats. These results demonstrate an attenuated responsiveness of sympathetic neural circuits to heating in senescent F344 rats.     

Forebrain and brain stem neural circuits contribute to altered sympathetic responses to heating in senescent rats.

Acute heating in young rats increases visceral sympathetic nerve discharge (SND); however, renal and splanchnic SND responses to hyperthermia are attenuated in senescent compared with young Fischer 344 (F344) rats (Kenney MJ and Fels RJ. Am J Physiol Regul Integr Comp Physiol 283: R513-R520, 2002). Central mechanisms by which aging alters visceral SND responses to heating are unknown. We tested the hypothesis that forebrain neural circuits are involved in suppressing sympathoexcitatory responses to heating in chloralose-anesthetized, senescent F344 rats. Renal and splanchnic SND responses to increased (38 degrees C-41 degrees C) internal temperature were determined in midbrain-transected (MT) and sham-MT young (3-mo-old), mature (12-mo-old), and senescent (24-mo-old) F344 rats and in cervical-transected (CT) and sham-CT senescent rats. Renal SND remained unchanged during heating in MT and sham-MT senescent rats but was increased in CT senescent rats. Splanchnic SND responses to heating were higher in MT vs. sham-MT senescent rats and in CT vs. MT senescent rats. SND responses to heating were similar in MT and sham-MT young and mature rats. Mean arterial pressure (MAP) was increased during heating in MT but not in sham-MT senescent rats, whereas heating-induced increases in MAP were higher in sham-MT vs. MT young rats. These data suggest that in senescent rats suppression of splanchnic SND to heating involves forebrain and brain stem neural circuits, whereas renal suppression is mediated solely by brain stem neural circuits. These results support the concept that aging alters the functional organization of pathways regulating SND and arterial blood pressure responses to acute heating.     

Differential pattern of spinal sympathetic outflow in response to stimulation of the caudal medullary raphe

In urethan-anesthetized cats, frequency domain analysis was used to explore the mechanisms of differential responses of inferior cardiac (CN), vertebral (VN), and renal (RN) sympathetic nerves to electrical stimulation of a discrete region of the medullary raphe (0-2 mm caudal to the obex). Raphe stimulation in baroreceptor-denervated cats at frequencies (7-12 Hz) that entrained the 10-Hz rhythm in nerve activity decreased CN and RN activities but increased VN activity. The reductions in CN and RN discharges were associated with decreased low-frequency (相似文献   

Frequency modulation of mesenteric and renal vascular resistance

The hypothesis was tested that low-frequency vasomotions in individual vascular beds are integrated by the cardiovascular system, such that new fluctuations at additional frequencies occur in arterial blood pressure. In anesthetized rats (n = 8), the sympathetic splanchnic and renal nerves were simultaneously stimulated at combinations of frequencies ranging from 0.075 to 0.8 Hz. Blood pressure was recorded together with mesenteric and renal blood flow velocities. Dual nerve stimulation at low frequencies (<0.6 Hz) caused corresponding oscillations in vascular resistance and blood pressure, whereas higher stimulation frequencies increased the mean levels. Blood pressure oscillations were only detected at the individual stimulation frequencies and their harmonics. The strongest periodic responses in vascular resistance were found at 0.40 +/- 0.02 Hz in the mesenteric and at 0.32 +/- 0.03 Hz (P < 0.05) in the renal vascular bed. Thus frequency modulation of low-frequency vasomotions in individual vascular beds does not cause significant blood pressure oscillations at additional frequencies. Furthermore, our data suggest that sympathetic modulation of mesenteric vascular resistance can initiate blood pressure oscillations at slightly higher frequencies than sympathetic modulation of renal vascular resistance.     

Patterning of somatosympathetic reflexes reveals nonuniform organization of presympathetic drive from C1 and non-C1 RVLM neurons

To determine the organization of presympathetic vasomotor drive by phenotypic populations of rostral ventrolateral medulla (RVLM) neurons, we examined the somatosympathetic reflex (SSR) evoked in four sympathetic nerves together with selective lesions of RVLM presympathetic neurons. Urethane-anesthetized (1.3 g/kg ip), paralyzed, vagotomized and artificially ventilated Sprague-Dawley rats (n = 41) were used. First, we determined the afferent inputs activated by sciatic nerve (SN) stimulation at graded stimulus intensities (50 sweeps at 0.5-1 Hz, 1-80 V). Second, we recorded sympathetic nerve responses (cervical, renal, splanchnic, and lumbar) to intensities of SN stimulation that activated A-fiber afferents (low) or both A- and C-fiber afferents (high). Third, with low-intensity SN stimulation, we examined the cervical SSR following RVLM microinjection of somatostatin, and we determined the splanchnic SSR in rats in which presympathetic C1 neurons were lesioned following intraspinal injections of anti-dopamine-β-hydroxylase-saporin (anti-DβH-SAP). Low-intensity SN stimulation activated A-fiber afferents and evoked biphasic responses in the renal, splanchnic, and lumbar nerves and a single peak in the cervical nerve. Depletion of presympathetic C1 neurons (59 ± 4% tyrosine hydroxylase immunoreactivity profiles lesioned) eliminated peak 2 of the splanchnic SSR and attenuated peak 1, suggesting that only RVLM neurons with fast axonal conduction were spared. RVLM injections of somatostatin abolished the single early peak of cervical SSR confirming that RVLM neurons with fast axonal conduction were inhibited by somatostatin. It is concluded that unmyelinated RVLM presympathetic neurons, presumed to be all C1, innervate splanchnic, renal, and lumbar but not cervical sympathetic outflows, whereas myelinated C1 and non-C1 RVLM neurons innervate all sympathetic outflows examined. These findings suggest that multiple levels of neural control of vasomotor tone exist; myelinated populations may set baseline tone, while unmyelinated neurons may be recruited to provide actions at specific vascular beds in response to distinct stressors.     

Coordination between cardiovascular and respiratory control systems during and after cerebral ischemia.

The dissociation of cardiovascular (arterial hypertension) and respiratory (depression) reactions to severe cerebral ischemia seems to be inconsistent with the usual cooperative behavior of the two systems and their role in managing disturbances in the central chemical environment. In the present study the Cushing reaction was elicited by transient increase of the intracranial pressure 4-11 times in each experiment. The pressor response and changes in the vertebral sympathetic nerve discharge (SND) were compared with the respiratory reaction and with changes in the phrenic nerve activity. The reaction in both nerves developed in two phases. In the phrenic nerve, an initial hyperactivity (increased discharge amplitude and frequency) coincided with augmentation of the rhythmic SND (phase 1) and complete nerve depression developed when the SND was desynchronized (phase 2). The transition in both systems correlated in their latencies and the severity of the ischemia needed for their stimulation. Repetition of the ischemic stimuli increased the occurrence of the respiratory-related rhythmicity in the SND and later changed its character from rhythmic amplitude modulation to respiratory-related high-frequency bursting SND coinciding with the inspiration. It is concluded that, despite the apparent dissociation between the cardiovascular and respiratory reactions, there is a parallel response between the neurophysiological correlates of the two systems to increasing severity of cerebral ischemia.     

Bacillus anthracis lethal toxin alters regulation of visceral sympathetic nerve discharge

Bacillus anthracis infection is a pathophysiological condition that is complicated by progressive decreases in mean arterial pressure (MAP). Lethal toxin (LeTx) is central to the pathogenesis of B. anthracis infection, and the sympathetic nervous system plays a critical role in physiological regulation of acute stressors. However, the effect of LeTx on sympathetic nerve discharge (SND), a critical link between central sympathetic neural circuits and MAP regulation, remains unknown. We determined visceral (renal, splenic, and adrenal) SND responses to continuous infusion of LeTx [lethal factor (100 μg/kg) + protective antigen (200 μg/kg) infused at 0.5 ml/h for ≤6 h] and vehicle (infused at 0.5 ml/h) in anesthetized, baroreceptor-intact and baroreceptor (sinoaortic)-denervated (SAD) Sprague-Dawley rats. LeTx infusions produced an initial state of cardiovascular and sympathetic nervous system activation in intact and SAD rats. Subsequent to peak LeTx-induced increases in arterial blood pressure, intact rats demonstrated a marked hypotension that was accompanied by significant reductions in SND (renal and splenic) and heart rate (HR) from peak levels. After peak LeTx-induced pressor and sympathoexcitatory responses in SAD rats, MAP, SND (renal, splenic, and adrenal), and HR were progressively and significantly reduced, supporting the hypothesis that LeTx alters the central regulation of sympathetic nerve outflow. These findings demonstrate that the regulation of visceral SND is altered in a complex manner during continuous anthrax LeTx infusions and suggest that sympathetic nervous system dysregulation may contribute to the marked hypotension accompanying B. anthracis infection.     

Simultaneous monitoring of acetylcholine and catecholamine release in the in vivo rat adrenal medulla

To simultaneously monitor acetylcholine release from pre-ganglionic adrenal sympathetic nerve endings and catecholamine release from post-ganglionic adrenal chromaffin cells in the in vivo state, we applied microdialysis technique to anesthetized rats. Dialysis probe was implanted in the left adrenal medulla and perfused with Ringer's solution containing neostigmine (a cholinesterase inhibitor). After transection of splanchnic nerves, we electrically stimulated splanchnic nerves or locally administered acetylcholine through dialysis probes for 2 min and investigated dialysate acetylcholine, choline, norepinephrine and epinephrine responses. Acetylcholine was not detected in dialysate before nerve stimulation, but substantial acetylcholine was detected by nerve stimulation. In contrast, choline was detected in dialysate before stimulation, and dialysate choline concentration did not change with repetitive nerve stimulation. The estimated interstitial acetylcholine levels and dialysate catecholamine responses were almost identical between exogenous acetylcholine (10 microM) and nerve stimulation (2 Hz). Dialysate acetylcholine, norepinephrine and epinephrine responses were correlated with the frequencies of electrical nerve stimulation, and dialysate norepinephrine and epinephrine responses were quantitatively correlated with dialysate acetylcholine responses. Neither hexamethonium (a nicotinic receptor antagonist) nor atropine (a muscarinic receptor antagonist) affected the dialysate acetylcholine response to nerve stimulation. Microdialysis technique made it possible to simultaneously assess activities of pre-ganglionic adrenal sympathetic nerves and post-ganglionic adrenal chromaffin cells in the in vivo state and provided quantitative information about input-output relationship in the adrenal medulla.     

Brain stem mechanisms underlying acupuncture modality-related modulation of cardiovascular responses in rats.

The present study was designed to investigate brain stem responses to manual acupuncture (MA) and electroacupuncture (EA) at different frequencies at pericardial P (5-6) acupoints located over the median nerve. Activity of premotor sympathetic cardiovascular neurons in the rostral ventral lateral medulla (rVLM) was recorded during stimulation of visceral and somatic afferents in ventilated anesthetized rats. We stimulated either the splanchnic nerve at 2 Hz (0.1-0.4 mA, 0.5 ms) or the median nerve for 30 s at 2, 10, 20, 40, or 100 Hz using EA (0.3-0.5 mA, 0.5 ms) or at approximately 2 Hz with MA. Twelve of 18 cells responsive to splanchnic and median nerve stimulation could be antidromically driven from the intermediolateral columns of the thoracic spinal cord, T2-T4, indicating that they were premotor sympathetic neurons. All 18 neurons received baroreceptor input, providing evidence of their cardiovascular sympathoexcitatory function. Evoked responses during stimulation of the splanchnic nerve were inhibited by 49 +/- 6% (n = 7) with EA and by 46 +/- 4% (n = 6) with MA, indicating that the extent of inhibitory effects of the two modalities were similar. Inhibition lasted for 20 min after termination of EA or MA. Cardiovascular premotor rVLM neurons responded to 2-Hz electrical stimulation at P 5-6 and to a lesser extent to 10-, 20-, 40-, and 100-Hz stimulation (53 +/- 10, 16 +/- 2, 8 +/- 2, 2 +/- 1, and 0 +/- 0 impulses/30 stimulations, n = 7). These results indicate that rVLM premotor sympathetic cardiovascular neurons that receive convergent input from the splanchnic and median nerves during low-frequency EA and MA are inhibited similarly for prolonged periods by low-frequency MA and EA.     

Rhythmic sympathetic nerve discharges in an in vitro neonatal rat brain stem-spinal cord preparation.

To understand the origination of sympathetic nerve discharge (SND), I developed an in vitro brain stem-spinal cord preparation from neonatal rats. Ascorbic acid (3 mM) was added into the bath solution to increase the viability of preparations. At 24 degrees C, rhythmic SND (recorded from the splanchnic nerve) was consistently observed, but it became quiescent at <16 degrees C. Respiratory-related SND (rSND) was discernible and was well correlated with C(4) root activity. Power spectral analysis of SND revealed a dominant 2-Hz oscillation. In most preparations (86%), such oscillation was persistent, whereas it only slightly reduced its magnitude after isolation from the brain stem. The removal of neural structures rostral to the superior cerebellar artery (equivalent to the level of facial nuclei) reduced rSND, increased tonic SND, but did not affect the temporal coupling between SND and C(4) root activity. Our data suggest a prominent contribution of SND from the neural mechanisms confined within the neonatal rat spinal cord. This ascorbic acid-enhanced in vitro preparation is a very useful model to study neural mechanisms underlying sympathorespiratory integration.     

Neuropeptides as central integrators of autonomic nerve activity: effects of TRH, SRIF, VIP and bombesin on gastric and adrenal nerves

The nerve activity of the gastric ramus of the splanchnic (sympathetic) nerve, gastric ramus of the vagus, adrenal ramus of the splanchnic nerve and the superior laryngeal nerve (laryngeal ramus of vagus) were assessed before and after i.c.v. injection of neuropeptides in the rat. TRH stimulated the vagal branch but attenuated the sympathetic outflow to the stomach. In contrast, the sympathetic outflow to the adrenal was enhanced by TRH. SRIF suppressed the activity of all the nerves studied. VIP did not affect the sympathetic outflow to the stomach while suppressing the gastric branch of the vagus. The adrenal sympathetic branch as well as the superior laryngeal nerve was stimulated by VIP. Bombesin suppressed both vagal and sympathetic outflow to the stomach but markedly stimulated the laryngeal branch of the vagus. The adrenal sympathetic nerve was either stimulated or attenuated slightly by bombesin. These results indicate that centrally administered neuropeptides produce reactions specific for each nerve.     

Renal sympathetic nerve regulation to heating is altered in rats with heart failure

Heart failure (HF) alters the regulation of basal sympathetic nerve discharge (SND); however, the effect of HF on SND responses to acute stress is not well established. In the present study, renal SND responses to hyperthermia were determined in chloralose-anesthetized HF rats and in sham controls. Whole body heating (colonic temperature increased from 38 to 41 degrees C) was used as an acute stressor because increased internal body temperature provides a potent stimulus to the sympathetic nervous system. Left ventricular end-diastolic pressure and the right ventricular wt-to-body wt ratio were increased (P < 0.05) in HF compared with sham rats. The following observations were made: 1) renal sympathoexcitatory responses to heating were significantly reduced in HF compared with sham rats, 2) renal blood flow remained unchanged from control levels during heating in HF rats but was significantly reduced in sham rats, and 3) renal SND responses to heating were significantly higher in HF rats with bilateral lesions of the hypothalamic paraventricular nucleus (PVN) compared with sham PVN-lesioned HF rats. These results demonstrate a marked attenuation in the responsiveness of renal SND to heating in HF rats and suggest that HF alters the organization of neural pathways mediating SND responses to heating.     

Effects of high-frequency oscillatory ventilation on vagal and phrenic nerve activities

This study was undertaken to define the mechanism for the respiratory inhibition observed during high-frequency oscillatory ventilation (HFOV). The effects of HFOV on the activities of single units in the vagus (Vna) and phrenic nerves (Pna) were examined in pentobarbital-anesthetized dogs. The animals were either ventilated by intermittent positive-pressure ventilation (IPPV) with and without positive end-expiratory pressure (PEEP), or by HFOV at a frequency of 25 Hz and pump displacement volume of 3 ml/kg. In 13 vagal units the Vna was much higher during HFOV than during IPPV or airway occlusion at a matched airway pressure. Ten units in the phrenic nerves were examined, and Pna (expressed as bursts/min) was attenuated by HFOV in all of them. In four of them, the effect of cooling the vagi to 8-10 degrees C on Pna was examined, and it was found that HFOV failed to alter the Pna. We conclude that 1) HFOV stimulates the pulmonary vagal afferent fibers continuously and to a degree greater than that due to static lung inflation and increased airway pressure and 2) the increased vagal activity during HFOV probably causes phrenic nerve activity inhibition.