Arterial Chemoreflex Research Articles

Differential effects of cardiac sympathetic afferent stimulation on neurons in the nucleus tractus solitarius

Activation of the cardiac “sympathetic afferent” reflex (CSAR) has been reported to depress the arterial baroreflex and enhance the arterial chemoreflex via a central mechanism. In the present study, we used single-unit extracellular recording techniques to examine the effects of stimulation of cardiac sympathetic afferents on baro- or chemosensitive neurons in the nucleus tractus solitarius (NTS) in anesthetized rats. Of 54 barosensitive NTS neurons tested for their response to epicardial application of capsaicin (0.4 μg), 38 were significantly ( P < 0.01) inhibited by 38% while 16 did not respond. Of 42 NTS chemosensitive neurons tested for their response to capsaicin, 33 were significantly ( P < 0.01) excited by 47% while 9 did not respond. In addition, of 12 both barosensitive and chemosensitive NTS neurons tested for capsaicin, 2 were excited, 7 were inhibited, and 3 did not respond. In conclusion, this study indicates that CSAR activation inhibited NTS barosensitive neurons and excited NTS chemosensitive neurons, suggesting that the NTS plays an important role in processing the interactions between these cardiovascular reflexes.

A “love triangle” elicited by electrochemistry: complex interactions among cardiac sympathetic afferent, chemo-, and baroreflexes

there are three major cardiovascular reflexes: the baroreflex, chemoreflex, and cardiac sympathetic afferent reflex (CSAR). This commentary provides a brief overview of these three reflexes and also discusses the interplay among them. In addition, it outlines the potential centrally integrative

Targeting Arterial Chemoreceptor Over-Activity in Heart Failure With a Gas

See related article, pages 260–267 With an aging population the prevalence of heart failure (HF) continues to rise. In the United States almost 5 million people experience HF, often with a poor prognosis resulting in 20% of patients dying within 1 year and ≈80% mortality within 8 years.1 Although the mechanisms underpinning cardiac failure are not firmly established, several converging events ranging from depressed contractility itself,2 diastolic dysfunction,3 failing energy stores,4 abnormal cell growth,3 and defective beta adrenergic signaling5 are implicated. Neurohumoral activation also appears to play a significant role in amplifying harmful substrate to trigger lethal ventricular arrhythmia which may account for ≈50% of all deaths that are sudden and unexpected.6 The precise role of abnormal neurohumoral signaling is still unclear but is thought to involve a synergistic activation of the sympathetic nervous system with the renin-angiotensin-aldosterone system7,8 and diminished parasympathetic activity.9 Emerging evidence now suggests that an aspect of impaired neurohumoral signaling in HF may arise from dysregulation of the arterial chemoreflex at the level of the carotid bodies by oxygen-free radicals. Stimulation of the carotid body (CB) arterial chemoreceptors provides an excitatory input to activate the sympathetic nervous system.10 Chronic HF causes a sustained activation of the sympathetic nervous system11 and is also associated with enhanced chemosensitivity in both clinical and experimental HF.12,13 The type I (glomus) cell of the CB is thought to be the primary chemoreceptor sensor. There is …

The Chemoreflex: Adult versus Child Comparison

Compare the influence of the chemoreflex on heart rate (HR) and blood pressure (BP) responses between children and adults. Seventy children (35 boys and 35 girls) and 70 adults (35 men and 35 women) performed 30% maximal voluntary contraction static handgrip exercise (SHG) for 3 min, followed by 4 min of muscle ischemia and then 6 min of recovery, while HR and BP were measured. During 3 min of SHG, systolic BP (SBP) increased significantly more in men versus boys (23+/-9 vs 18+/-9%) and women versus girls (21+/-10 vs 15+/-7%), respectively. Diastolic BP (DBP) increased similarly during SHG in adults versus children. During SHG, HR increased similarly in males but significantly more in girls versus women (16+/-10 vs 11+/-9%), respectively. During occlusion, HR fell to baseline and remained through recovery in adults and children. Both SBP and DBP decreased similarly during the first minute of occlusion but remained significantly above baseline in adults and children. During the first minute of recovery, BP decreased to baseline in adults. In children, DBP decreased but remained significantly above baseline through recovery. SBP decreased in children during minute 1 of recovery yet remained significantly above baseline for 1-2 min in children. The muscle chemoreflex influence on HR and BP is similar in children and adults as evident in the return of HR to baseline, with a similar concomitant maintenance of BP above baseline during occlusion. When occlusion is released, BP returns to baseline in adults, whereas in children DBP remains significantly above baseline through recovery and SBP for 1-2 min. The differing BP response may be explained by a more active arterial chemoreflex in children.

Discharge patterns of preganglionic neurones with axons in a cardiac vagal branch in the rat.

The fibre types that run in a vagal branch projecting to the rat heart are described in this study. In order to obtain spontaneous discharge in this vagal branch and optimal recording conditions, we compared the decerebrate state to urethane, urethane-chloralose and pentobarbital-chloralose anaesthesia with regard to level of chronotropic cardiac vagal tone. Administration of atropine (2 mg kg(-1), I.V.) significantly decreased baseline cardiac interval only in the decerebrate and urethane-anaesthetised rat (by 0.018 +/- 0.001 s and 0.019 +/- 0.002 s, respectively). As a result of these experiments, urethane was chosen as the anaesthetic for all subsequent studies. Using a heart rate signal-averaging method we demonstrated that rat cardiac vagal preganglionic neurones innervating the sinoatrial node should have an expiratory discharge pattern, as reported in other species. However, only 5 % of chronotropic vagal tone was found to be subject to respiratory sinus arrhythmia. A suction microelectrode method, combined with spike-triggered averaging, was employed to record activity from a total of 58 vagal afferents that had axons in this branch. Approximately 75 % of these latter sensory fibres displayed cardiac rhythm. In a separate study we also recorded 318 preganglionic neurones with axons in the right cardiac vagal branch of the rat. Respiratory-modulated preganglionic units were statistically less common than tonically firing units. Six preganglionic subtypes were categorised according to conduction velocity and respiratory discharge pattern. Myelinated B-fibre and unmyelinated C-fibre types were found to be equally prevalent and equally likely to be reflexly excited during the pulmonary chemoreflex and the peripheral arterial chemoreflexes. The electrophysiological analysis has shown how diverse the discharge patterns of the preganglionic neurones or interneurones are whose axons course in the right cardiac vagal branch of the rat. The results of these experiments demonstrate the usefulness of combining spike discrimination with multiple spike-triggered averaging to simultaneously record B and C centrifugal vagal efferents.

Differential Changes in Dopamine D2- and D1-Receptor mRNA Levels Induced by Hypoxia in the Arterial Chemoreflex Pathway Organs in One-Day-Old and Adult Rabbits

This study determined: (1) whether dopamine (DA) D₂-receptor (R) and D₁-R mRNA levels in the carotid body (CB), petrosal ganglion (PG) and superior cervical ganglion (SCG) are modulated by hypoxia; (2) the role of hypoxia intensity and exposure duration, and (3) whether the pattern of modulation differs between newborn (1-day-old) and adult rabbits. Rabbits were exposed to five F_iO₂ conditions: 21% (control); 15%/6 h; 15%/24 h; 8%/6 h and 8%/24 h. D₂- and D₁-R mRNA expression levels were calculated for each hypoxia condition relative to control using RT-PCR analysis. In the CB of 1-day-old rabbits, D₂- and D₁-R transcript levels increased and decreased after exposure to 15 and 8% O₂, respectively. In the adult CB, D₂- and D₁-R transcript levels decreased independently of hypoxia intensities. Only changes in D₁-R mRNA levels were dependent on exposure time. In the PG, both hypoxia intensities decreased the D₂-R transcript levels in 1-day-old and adult rabbits; but for the D₁-R mRNA levels, hypoxia decreased its level in 1-day-old rabbits and increased it in adults regardless of exposure duration. In the SCG, hypoxia had no determinant effect on the D₂-R mRNA levels either in newborn or adult rabbits while it induced a decrease of D₁-R transcript levels in 1-day-old rabbits and an increase in adult rabbits. It is concluded that hypoxia affects DA D₂- or D₁-R mRNA levels in the chemoreflex pathway in an age-dependent and site-specific manner.

C-Fos expression in the midbrain periaqueductal gray after chemoreceptor and baroreceptor activation.

The pattern of Fos-like immunoreactivity (FLI) in the periaqueductal gray (PAG) associated with activation of arterial chemoreceptors versus baroreceptor afferents was examined in urethane-anesthetized rats. Chemoreflex responses elicited by repeat intravenous injections of potassium cyanide (KCN; 90 microg/kg) significantly increased FLI in all columns of the PAG relative to saline-injected animals. Pressor responses elicited by intravenous phenylephrine (PE) produced a similar pattern of increased FLI throughout the PAG except in the dorsomedial and lateral columns of the caudal PAG, where FLI was minimal. Chemoreflex responses were unaltered by blockade of excitatory amino acid receptors in the dorsomedial PAG, and < 10% of the neurons of the caudal PAG that expressed FLI after KCN stimulation were retrogradely labeled from the A5 region of the caudal ventrolateral pons. These results indicate that integration of chemoreceptor inputs occurs primarily in the dorsal and lateral columns of the caudal PAG, but these neurons have little direct descending influence over lower brain stem regions integral to the central arterial chemoreflex arc.

Cellular distribution of oxygen sensor candidates-oxidases, cytochromes, K+-channels--in the carotid body.

The specific tissue of the carotid body is built up of groups of glomus cells, enveloped by glial-type sustentacular cells, and innervated by sensory nerve fibers. These units sense arterial pO(2) and respond to hypoxia by a variety of reactions that include initiation of the arterial chemoreflex, i.e., increasing firing activity in the carotid sinus nerve. Until now, neither the cellular localization of the initial events that lead to stimulation of chemoreceptor afferents nor the molecular mechanism of oxygen sensing in the carotid body have been unequivocally identified. Proposed molecular candidates for the mechanism of oxygen sensing include: 1). components of the mitochondrial respiratory chain, 2). NADPH oxidases generating reactive oxygen species in an oxygen-dependent manner, 3). oxygen-regulated plasmalemmal K(+)-channels, and 4). nonoxidase iron-proteins. Our still limited knowledge on their cellular distribution within the carotid body is reviewed here. It is evident that: 1). the distribution of at least some oxygen sensor candidates is not ubiquitous but cell-type-specific, and 2). each specific parenchymal cell type of the carotid body contains at least one of the proposed oxygen sensor candidates. This applies also for the glial-type sustentacular cells that exhibit immunoreactivity to the two-pore domain K(+)-channel, TASK-1. These observations fit best with the assumption that each cell type within the carotid body is principally responsive to hypoxia. The differential equipping of glomus cells, nerve endings, and sustentacular cells with sensor proteins might serve to determine different thresholds of sensitivity and/or to connect the process of oxygen sensing to different signaling pathways. It also favors the assumption that several mechanisms of oxygen sensing may act simultaneously. The cellular identification of the cell type initiating the chemoreceptor reflex, however, has to await the molecular identification of the particular oxygen sensor molecule that initiates increased carotid sinus nerve activity.

Interactive effect of hypoxia and otolith organ engagement on cardiovascular regulation in humans.

We determined the interaction between the vestibulosympathetic reflex and the arterial chemoreflex in 12 healthy subjects. Subjects performed three trials in which continuous recordings of muscle sympathetic nerve activity (MSNA), mean arterial blood pressure (MAP), heart rate (HR), and arterial oxygen saturation were obtained. First, in prone subjects the otolith organs were engaged by use of head-down rotation (HDR). Second, the arterial chemoreflex was activated by inspiration of hypoxic gas (10% O2 and 90% N2) for 7 min with HDR being performed during minute 6. Third, hypoxia was repeated (15 min) with HDR being performed during minute 14. HDR [means +/- SE; increase (Delta)7 +/- 1 bursts/min and Delta50 +/- 11% for burst frequency and total MSNA, respectively; P < 0.05] and hypoxia (Delta6 +/- 2 bursts/min and Delta62 +/- 29%; P < 0.05) increased MSNA. Additionally, MSNA increased when HDR was performed during hypoxia (Delta11 +/- 2 bursts/min and Delta127 +/- 57% change from normoxia; P < 0.05). These increases in MSNA were similar to the algebraic sum of the individual increase in MSNA elicited by HDR and hypoxia (Delta13 +/- 1 bursts/min and Delta115 +/- 36%). Increases in MAP (Delta3 +/- 1 mmHg) and HR (Delta19 +/- 1 beats/min) during combined HDR and hypoxia generally were smaller (P < 0.05) than the algebraic sum of the individual responses (Delta5 +/- 1 mmHg and Delta24 +/- 2 beats/min for MAP and HR, respectively; P < 0.05). These findings indicate an additive interaction between the vestibulosympathetic reflex and arterial chemoreflex for MSNA. Therefore, it appears that MSNA outputs between the vestibulosympathetic reflex and arterial chemoreflex are independent of one another in humans.

Cardiovascular responses to chemoreflex activation with potassium cyanide or hypoxic hypoxia in awake rats

Although intravenous (iv) injection of potassium cyanide (KCN) activates the arterial chemoreflex, it has been questioned whether cytotoxic hypoxia reproduces a physiological stimulus such as hypoxic hypoxia (low inspired O 2 tension). Thus, the goal of the present study was to compare the cardiovascular responses elicited by intravenous injection of KCN to those caused by hypoxic hypoxia in awake rats before and after bilateral ligature of carotid body arteries. We tested the hypothesis that hypoxic hypoxia activates the cardiovascular chemoreflex just as KCN does, causing an increase in arterial pressure and bradycardia. Intact adult Wistar rats received an intravenous injection of KCN (160 μg/kg) and were exposed to hypoxic hypoxia (7–5% O 2 breathing) for 10–15 s at random while mean arterial pressure (MAP) and heart rate (HR) were measured. After the experiments, the animals were submitted to bilateral ligature of carotid body arteries or sham operation and the protocol was repeated on the subsequent day. Before surgery, all rats showed an abrupt rise in arterial pressure accompanied by a marked bradycardia in response to KCN or hypoxic hypoxia, with a very similar pattern. After surgery, these responses persisted only in the sham-operated group and were totally abolished in the ligature group. In conclusion, our data show that KCN is an appropriate stimulus to activate arterial chemoreflex because its cardiovascular responses are comparable to those induced by hypoxic hypoxia. Thus, the use of KCN as a tool to evaluate different aspects of the complex pattern of cardiovascular, respiratory, and behavioural responses to chemoreflex activation seems to be physiologically acceptable.

Evidence for alpha-2 adrenoreceptor modulation of arterial chemoreflexes in the caudal solitary nucleus of the rat.

The caudal region of the nucleus of the solitary tract (cNTS) is the primary central termination site for arterial chemoreceptor afferents originating from the carotid body. The purpose of the present study was to investigate the role of endogenous activation of alpha-2 adrenoreceptors in the cNTS on arterial chemoreflex function. Arterial chemoreflex responses to intravenous injections of potassium cyanide (KCN; 75 microg/kg) were recorded before and following blockade of alpha-2 adrenoreceptors in the cNTS of urethane-anesthetized rats. KCN alone elicited a reflex increase in arterial pressure, renal sympathetic nerve activity, and respiration. After bilateral cNTS microinjection of alpha-2 receptor antagonists (2 nmol idazoxan or 0.2 nmol yohimbine), arterial chemoreflex responses were markedly attenuated. Attenuation of chemoreflex function was not accompanied by any significant change in resting blood pressure or respiratory rate. The results suggest that the endogenous activation of alpha-2 adrenoreceptors facilitates central processing of chemoreceptor afferent inputs in the cNTS of the rat.

Marked sympathetic activation in patients with chronic respiratory failure.

The autonomic nervous system may be disturbed in chronic respiratory failure. We tested the hypothesis that there is increased sympathetic activity in patients with chronic hypoxemia. Furthermore, we examined the effect of short-term oxygen on muscle sympathetic nerve activity (MSNA) in these patients. We performed microneurography of the peroneal nerve in 11 patients with hypoxemia due to chronic obstructive pulmonary disease (COPD, n = 6) or lung fibrosis (n = 5) and in 11 healthy subjects matched for age and sex. MSNA was measured during normal breathing in all subjects. In eight patients and in seven control subjects, MSNA was also measured during nasal oxygen (4 L/min). MSNA was higher in the patients with chronic respiratory failure compared with the healthy subjects during normal breathing (61 +/- 5 versus 34 +/- 2 bursts/min, mean +/- SEM; p = 0.0002, paired t test). During oxygen administration, MSNA decreased from 63 +/- 6 to 56 +/- 6 bursts/min in the patients (p = 0.0004, ANOVA); there was no change in sympathetic activity in the control subjects. For the first time, there is direct evidence of marked sympathetic activation in patients with chronic respiratory failure. This is partly explained by arterial chemoreflex activation and may play an important role in the pathogenesis of the disease.

Time-dependent changes in dopamine D 2-receptor mRNA in the arterial chemoreflex pathway with chronic hypoxia

The hypoxic ventilatory response (HVR) can be modulated by dopamine D 2-receptors (D 2-R) in both the carotid body arterial chemoreceptors and the nucleus tractus solitarius (NTS), the primary synapse site of carotid body afferents. We hypothesized that chronic hypoxia alters D 2-R gene expression to initiate changes in D 2-R modulation of the HVR and enhance ventilatory acclimatization to hypoxia. Thus, we used a competitive reverse transcription-polymerase chain reaction (RT-PCR) method to quantify changes in D 2-R mRNA levels in the rat carotid body and NTS after 0, 6, 12, 24, 48, or 168 h of hypobaric hypoxia ( P IO 2 =80 Torr). In the rostral NTS, hypoxia significantly increased D 2-R mRNA at all time points. In the caudal NTS, D 2-R mRNA levels initially increased in response to hypoxia and then significantly decreased to 71±5% and 71±6% of control after 48 and 168 h of hypoxia, respectively. In the carotid body, D 2-R mRNA levels significantly decreased to 59±2% of control after 48 h of hypoxia; however, they significantly increased to 274±22% of control after 168 h. These results suggest that changes in D 2-R mRNA in the arterial chemoreflex pathway and corresponding changes at the protein and signaling levels may contribute to the time-dependent changes in ventilation observed with chronic hypoxia. Specifically, decreased carotid body inhibition by D 2-R could increase the HVR after 2 days of hypoxia.

Is the aortic depressor nerve involved in arterial chemoreflexes in rats?

Recent anatomical and physiological studies showed that chemoreceptor afferent fibers are present in the rat aortic depressor nerve (ADN), which has been considered to contain exclusively baroreceptor afferent fibers. However, it remains to be proven whether the chemoreceptor afferents of the ADN are practically involved in chemoreflexes. The present study was performed in chloralose/urethane-anesthetized rats of either Sprague–Dawley (SD) or Wistar strain to examine whether the ADN carries sufficient information regarding arterial hypoxia and hypercapnia, and whether the ADN indeed participates in chemoreflexes, the circulatory and respiratory components. It was found in either strain that afferent discharges of the ADN were not affected at all by hypoxia or hypercapnia, whereas those of the carotid sinus nerve (CSN) markedly increased due to these stimuli. Hypoxia produced hypertension, transient bradycardia followed by tachycardia, and respiratory facilitation, which characterize the chemoreflexes. Any of these responses was not affected at all by the ADN section, but all were abolished by the CSN section. Intraaortic injection of cyanide also induced transient bradycardia and respiratory facilitation, but any of them was not affected by the ADN section while all were abolished by the CSN section. Furthermore, electrical stimulation of the ADN produced solely baroreflex responses, i.e. hypotension and respiratory suppression, whereas that of the CSN provoked chemoreflex responses, i.e. early, transient hypertension and respiratory facilitation. In conclusion, the rat ADN does not contain a functionally significant number of chemoreceptor afferent fibers, if at all, and does not appreciably contribute to generation of chemoreflexes.

Arterial chemoreflex in conscious normotensive and hypertensive adult rats.

Evidence from human and animal studies suggests that the arterial chemoreflex may be exaggerated in essential hypertension. In the present study, cardiorespiratory responses to peripheral chemoreceptor stimulation were compared in conscious unrestrained spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats (13-14 wk old). Chemoreceptors were stimulated by injections of potassium cyanide (30-125 microgram/kg iv). Chemoreceptor stimulation elicited a pressor response and bradycardia. The peak change in mean arterial pressure evoked during chemoreceptor stimulation was not significantly different between SH (n = 18) and WKY (n = 18) rats but was significantly smaller in SD rats (n = 18). An evaluation of respiratory responses to chemoreceptor stimulation in conscious and anesthetized rats also demonstrated no significant difference between SH and WKY rats, but the response of the SD rats tended to be smaller. These results demonstrate that differences in the arterial chemoreflex response of SH vs. normotensive rats are not linked to hypertension but, rather, to differences between rat strains.

Expression of dopamine D1-receptor mRNA in the carotid body of adult rabbits, cats and rats

Dopamine is a major neurotransmitter in the carotid body of several animal species and its functional role at the level of peripheral arterial chemoreflex pathway is attributed to the presence of the dopamine D2-receptors. We present evidence that the dopamine D1-receptor mRNA is also expressed in the carotid body of adult rabbits, cats and rats. A DNA fragment of 611 bp of this receptor was first isolated from rabbit. The nucleic acid sequence of this fragment was found to be 84.5% identical to that of rat. This specific 611 bp fragment was used as a probe to detect, either by Northern analysis or by the reverse transcription-polymerase chain reaction, the dopamine D1-receptor mRNA. The results revealed the presence of dopamine D1-receptor transcript in the carotid body as well as in the petrosal ganglion and the superior cervical ganglion from the three animal models studied here. The physiological significance of dopamine D1-receptor expression in the carotid body is discussed.

Potassium and breathing in exercise.

The increase in ventilation caused by exercise is controlled by a combination of neural and chemical events, although the precise contribution and relative importance of these signals is still debated. It is generally agreed that the genesis of exercise hyperpnoea lies within the central nervous system and that peripheral reflexes, both chemical and neural, modulate central drive. Recently, attention has once again focused on the idea that circulating factors, in particular potassium, may play an important role in this modulation by stimulating known areas of peripheral chemoreception. Arterial chemoreceptors, muscle chemoreflex and slowly adapting pulmonary stretch receptors are all excited by hyperkalaemia. When potassium is raised to mimic exercise concentrations it increases ventilation in anaesthetised animals. This response is abolished by surgical denervation of the arterial chemoreceptors and is markedly reduced by chemical denervation with hyperoxia. Hypoxia enhances the ventilatory response to hyperkalaemia, and the stimulatory effects of potassium are further increased when combined with lactic acid or raised concentrations of noradrenaline. Hyperkalaemia can also increase the hypoxic sensitivity of the arterial chemoreflex in exercise. There is a close temporal relationship between potassium and ventilation during exercise, but changes in potassium are not proportionally related to changes in ventilation. When all data are taken together, there is good evidence that potassium has a supporting role in the control of exercise hyperpnoea, predominantly through modulation of the arterial chemoreflex.

Ethanol inhibits chemoreflex excitation of reticulospinal vasomotor neurons

In anesthetized and ventilated rats, activation of carotid chemoreceptors with intracarotid administration of 100 nmol sodium cyanide rapidly excited the spinal cord-projecting vasomotor neurons in the rostroventrolateral reticular nucleus (RVL) of the medulla oblongata and sympathetic nerves and increased arterial pressure. The chemoreflex symphthoexcitatory pressor responses were attenuated by an acute systemac administration of ethanol at 0.45 g/kg, but not at 45 mg/kg. The ethanol effects were observed at the level of RVL-spinal vasomotor neurons, in attenuating the neuronal responses to the chemoreflex excitation and direct iontophoresis of N-methyl-d-aspartic acid (NMDA) but without altering responses of the carotid sinus nerves to intracarotid cyanide. The effect of ethanol on the RVL neurons was further defined as blocking NMDA-evoked inward current in the corresponding spontaneously active RVL neurons in vitro. The results indicate that acute ethanol intoxication markedly influences NMDA receptor activation and arterial chemoreflexes. The relevance of the type of action to clinical hypertension in chronic and heavy drinkers is discussed.

Ethanol inhibits chemoreflex excitation of reticulospinal vasomotor neurons

In anesthetized and ventilated rats, activation of carotid chemoreceptors with intracarotid administration of 100 nmol sodium cyanide rapidly excited the spinal cord-projecting vasomotor neurons in the rostroventrolateral reticular nucleus (RVL) of the medulla oblongata and sympathetic nerves and increased arterial pressure. The chemoreflex symphthoexcitatory pressor responses were attenuated by an acute systemac administration of ethanol at 0.45 g/kg, but not at 45 mg/kg. The ethanol effects were observed at the level of RVL-spinal vasomotor neurons, in attenuating the neuronal responses to the chemoreflex excitation and direct iontophoresis of N-methyl- d-aspartic acid (NMDA) but without altering responses of the carotid sinus nerves to intracarotid cyanide. The effect of ethanol on the RVL neurons was further defined as blocking NMDA-evoked inward current in the corresponding spontaneously active RVL neurons in vitro. The results indicate that acute ethanol intoxication markedly influences NMDA receptor activation and arterial chemoreflexes. The relevance of the type of action to clinical hypertension in chronic and heavy drinkers is discussed.

Surges of muscle sympathetic nerve activity during obstructive apnea are linked to hypoxemia

Obstructive sleep apnea (OSA) is associated with oscillations of arterial blood pressure (BP) that occur in phase with irregularities of respiration. To explore the role of the sympathetic nervous system in these responses, we studied muscle sympathetic nerve activity (MSNA; peroneal microneurography), an index of vasoconstrictor nerve traffic, and BP during awake regular breathing and during spontaneous apneas in patients with OSA. To determine the role of the arterial chemoreflex, we also examined the effects of 100% O2 (hyperoxia) on MSNA and BP. In awake regularly breathing patients with OSA (n = 12), resting MSNA was markedly higher than in an age-matched control population (n = 15) [41 +/- 23 (SD) vs. 24 +/- 17 bursts/min; P < 0.05] and was unchanged during hyperoxia (n = 9). Apneas during sleep (n = 8) were associated with surges in MSNA followed by transient rises in BP when breathing resumed. In contrast to room air apneas, hyperoxic apneas of similar duration were associated with attenuated MSNA responses (+82 +/- 84% vs. +5 +/- 25% compared with awake baseline; P < 0.05; n = 6), even though O2 did not affect sleep stage and the occurrence of arousal. Thus the BP oscillations that occur with apnea during sleep may in part be mediated by intermittent surges of sympathetic activity resulting in vasoconstriction. Because the MSNA responses to obstructive apnea are blunted during O2 administration, they appear to be linked to intermittent arterial hypoxemia and stimulation of arterial chemoreceptors.