Arterial Chemoreceptor Reflex Research Articles

Relaxin‐3 receptor (RXFP3) mediated modulation of central respiratory activity

The neuropeptide, relaxin‐3, is expressed by pontine nucleus incertus (NI) neurons. Relaxin‐3 and synthetic agonist peptides modulate arousal and cognitive processes via activation of the rela xin‐ family peptide 3 receptor (RXFP3). We recently demonstrated that a double‐chain RXFP3 peptidomimetic (RXFP3‐A2) in the nucleus of the solitary tract (NTS) triggered a mild stimulation of respiration and augmented the chemoreceptor reflex in an in situ perfused brainstem preparation ( Furuya et al., 2020). In the present study, we assessed the central respiratory effects of systemic application and local microinjection into the NTS, Kölliker‐Fuse nucleus (KF) or NI of a single chain RXFP3 peptidomimetic (B18) in the perfused brainstem preparation.Systemic application of B18 (2 μM) triggered a dose‐dependent increase in respiratory rate by 22 ± 8%. At this concentration of B18, the NaCN‐evoked (0.1% w/v, 100 μl, bolus injection) tachycardia of the arterial chemoreceptor reflex was augmented by 95 ± 14% compared to control (p<0.001, n=4). Local microinjections into the NTS also increased respiratory frequency (28 ± 5%, p<0.05, n=6) and enhanced the NaCN‐evoked tachycardia by 59%. Microinjections into the KF only triggered a mild increase in respiratory frequency (18 ± 7%, p<0.05, n=6) but had no effect on the NaCN‐evoked chemoreceptor reflex. Finally, microinjections into the NI (n=6) had no effect on either stationary breathing activity, or on the chemoreceptor reflex. We conclude that relaxin‐3 neurons target RXFP3 in respiratory control areas and acts as a general respiratory stimulant, causing mild increases in respiratory frequency. Importantly, RXFP3 stimulation significantly enhanced the respiratory response of arterial chemoreceptor reflex, implicating a major neuromodulatory role in this specific reflex pathway.

Relaxin-3 receptor (RXFP3) activation in the nucleus of the solitary tract modulates respiratory rate and the arterial chemoreceptor reflex in rat

The neuropeptide relaxin-3 is expressed by the pontine nucleus incertus. Relaxin-3 and synthetic agonist peptides modulate arousal and cognitive processes via activation of the relaxin-family peptide 3 receptor (RXFP3). Despite the presence of RXFP3 in the nucleus of the solitary tract (NTS), the ability of RXFP3 to modulate NTS-mediated cardiorespiratory functions has not been explored. Therefore, we examined the effects of bilateral microinjections of the selective agonist, RXFP3-A2 (40 μM, 100 nL/side), into the NTS in perfused working-heart-brainstem-preparations from rats (n = 6), while recording phrenic, vagal, and thoracic sympathetic chain activity (PNA, VNA, t-SCA) and heart rate (HR). RXFP3-A2 significantly increased respiratory rate and shortened post-inspiratory VNA. RXFP3-A2 in the NTS also significantly enhanced arterial chemoreceptor reflex (a-CR)-mediated tachypnea. However, RXFP3-A2 had no significant effect on HR and t-SCA at baseline or during the a-CR. These data represent the first evidence that RXFP3 activation in the NTS can selectively modulate respiration at baseline and during reflex behaviour.

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

Ablation of NK 1 receptor bearing neurons in the nucleus of the solitary tract blunts cardiovascular reflexes in awake rats

The nucleus of the solitary tract (NTS) receives primary afferents involved in cardiovascular regulation. We investigated the role of NK 1-receptor bearing neurons in the NTS on cardiovascular reflexes in awake rats fitted with chronic venous and arterial cannulae. These neurons were lesioned selectively with saporin conjugated with substance P (SP-SAP, 2 μM, bilateral injections of 20 nL in the subpostremal NTS, or 200 nL in both the subpostremal and the commissural NTS). Before, and 7 and 14 days after injection of SP-SAP, we measured changes in blood pressure and heart rate induced by i.v. injection of phenylephrine and nitroprusside (baroreceptor reflex), cyanide (arterial chemoreceptor reflex), and phenylbiguanide (Bezold-Jarisch reflex). The smaller injections with SP-SAP completely abolished NK1 receptor staining in the subpostremal NTS. The larger injections abolished NK1 receptor immunoreactivity in an area that extended from the commissural NTS to the rostral end of the subpostremal NTS. The lesions seemed to affect only a limited number of neurons, since neutral red stained sections did not show any obvious reduction in cell number. The smaller lesions reduced the gain of baroreflex bradycardia and the hypotension induced by phenylbiguanide. The larger lesions completely abolished the response to phenylbiguanide, blocked the baroreflex bradycardia induced by phenylephrine, severely blunted the baroreflex tachycardia, and blocked the bradycardia and reduced the hypertension induced by cyanide. Thus, these responses depend critically on NK 1-receptor bearing neurons in the NTS.

Inhibition of neurons in commissural nucleus of solitary tract reduces sympathetic nerve activity in SHR.

Neurons in the commissural nucleus of the solitary tract (commNTS) play an important role in certain cardiovascular responses dependent on sympathetic vasoconstrictor activation, including the arterial chemoreceptor reflex. Electrolytic lesions of the commNTS elicit a fall in arterial pressure (AP) in spontaneously hypertensive rats (SHR). To determine whether the latter result 1) arose from elimination of commNTS neuronal activity rather than en passant axons and 2) was accompanied by a reduction in sympathetic nerve activity, we evaluated the effect of inhibition of neurons in the commNTS on basal splanchnic sympathetic nerve activity (SNA), AP, and heart rate (HR) in SHR, Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats. In chloralose-anesthetized, paralyzed, and artificially ventilated SHR, microinjection of GABA into the commNTS markedly decreased splanchnic SNA, AP, and HR. The reductions in SNA and AP following similar microinjections in WKY and SD rats were significantly less than those in SHR. Our findings suggest that tonically active neurons in the commNTS contribute to the maintenance of SNA and the hypertension in SHR. The level of tonic discharge of these commNTS neurons in normotensive WKY and SD rats may be lower than in SHR.

Differential chemoreceptor reflex responses of adrenal preganglionic neurons.

Adrenal sympathetic preganglionic neurons (ADR SPNs) regulating the chromaffin cell release of epinephrine (Epi ADR SPNs) and those controlling norepinephrine (NE ADR SPNs) secretion have been distinguished on the basis of their responses to stimulation in the rostral ventrolateral medulla, to glucopenia produced by 2-deoxyglucose, and to activation of the baroreceptor reflex. In this study, we examined the effects of arterial chemoreceptor reflex activation, produced by inhalation of 100% N(2) or intravenous injection of sodium cyanide, on these two groups of ADR SPNs, identified antidromically in urethane-anesthetized, artificially ventilated rats. The mean spontaneous discharge rates of 38 NE ADR SPNs and 51 Epi ADR SPNs were 4.4 +/- 0.4 and 5.6 +/- 0.4 spikes/s at mean arterial pressures of 98 +/- 3 and 97 +/- 3 mmHg, respectively. Ventilation with 100% N(2) for 10 s markedly excited all NE ADR SPNs (+222 +/- 23% control, n = 36). In contrast, the majority (40/48; 83%) of Epi ADR SPNs were unaffected or slightly inhibited by ventilation with 100% N(2) (population response: +6 +/- 10% control, n = 48). Similar results were obtained after injection of sodium cyanide. These observations suggest that the network controlling the spontaneous discharge of NE ADR SPNs is more sensitive to brief arterial chemoreceptor reflex activation than is that regulating the activity of Epi ADR SPNs. The differential responsiveness to activation of the arterial chemoreceptor reflex of the populations of ADR SPNs regulating epinephrine and norepinephrine secretion suggests that their primary excitatory inputs arise from separate populations of sympathetic premotor neurons and that a fall in arterial oxygen tension is not a major stimulus for reflex-mediated adrenal epinephrine secretion.

Postexercise decrease in arterial blood pressure, total peripheral resistance and in circulatory responses to brief hyperoxia in subjects with mild essential hypertension.

The objective of our study was: (1) to compare the influence of moderate exercise on circulatory after-response in mildly hypertensive (n = 8) and normotensive male subjects (n = 9); (2) to examine the circulatory response to 3-min hyperoxic inactivation of arterial chemoreceptors at rest and during postexercise period in both groups. Hypertensive men (HTS) with a systolic blood pressure (SBP) 148 +/- 5 mm Hg, diastolic blood pressure (DBP) 92.4 +/- 4 mm Hg; and normotensive men (NTS), with a SBP 126 +/- 3 mm Hg, DBP 75.6 +/- 1.3 mm Hg, were submitted to 20-min of moderate exercise on a cycloergometer (up to the level of 55% of each subject's resting heart rate reserve). Finger arterial BP was recorded continuously with Finapres, impedance reography was used for recording stroke volume, cardiac output and arm blood flow. In HTS a significant decrease in SBP by 14.5 +/- 3.4 mm Hg, DBP by 8.9 +/- 1.9 mm Hg, total peripheral resistance (TPR) by 0.45 +/- 0.05 TPR u. (33.7 +/- 2.7%), and in arm vascular resistance (AVR) by 11.0 +/- 2.7 PRU u. (35.6 +/- 7%), was observed over a 60-min postexercise period. NTS exhibited insignificant changes in SBP, DBP, AVR except a significant decrease in TPR limited only to 20-min postexercise period. Hyperoxia decreased SBP, DBP and TPR in HTS. This effect was significantly attenuated during the postexercise period. Long-lasting antihypertensive effect of a single dynamic exercise in HTS suggests that moderate exercise may be applied as an effective physiological procedure to reduce elevated arterial BP in mild hypertension. We suggest also that the attenuation of the sympathoexcitatory arterial chemoreceptor reflex may contribute to a postexercise decrease in arterial BP and in TPR in mildly hypertensive subjects.

Effects of acute hypoxia and hyperoxia on ventilation in spontaneously hypertensive and normotensive rat

The aim of this study was to investigate whether there are differences between particular characteristics of the ventilatory responses to acute hypoxia and hyperoxia in primary hypertensioe and notmotensive states which might indicate significant differences in arterial chemoreceptor reflex function. Pneumotachographic monitoring of ventilation was carried out in anesthetized, spontaneously breathing, normotensive randomly bred Wistar rats (NWR), Wistar-Kyoto rats (WKY) and spontaneously hypertensioe rats (SHR). Under air breathing conditions, minute ventilation in SHR (50 ± 2 ml/min per 100 g) was not significantly different from that of WKY (54 ± 3 ml/min per 100 g) but NWR had a significantly lower minute ventilation (39 ± 1 ml/min per 100 g) than both SHR and WKY. Our data indicate that there is no elevation of the ventilatory drive under air breathing conditions which can be unequivocally associated with primary hypertension in adult animals. During acute hypoxia, minute ventilation increased by a similar magnitude in SHR and NWR (by 97 and 77%, respectively, above baseline values), whereas in WKY the increase was only 58%. When exposed to acute hyperoxia, minute ventilation was inhibited by a similar degree in all animals investigated. We conclude that there is no characteristic pattern of peripheral chemoreceptor-mediated ventilatory responses in close association with primary hypertension.

Effect of arterial chemoreceptor stimulation with almitrine bismesylate on plasma renin activity, aldosterone, ACTH and cortisol in anaesthetized, artificially ventilated cats.

1. Changes in plasma renin activity (PRA) and in the plasma concentration of aldosterone, adrenocorticotrophic hormone (ACTH) and cortisol in response to an intravenous infusion of the chemoreceptor stimulant almitrine bismesylate (0.2 mg/kg) were studied in two groups of anaesthetized, paralysed and constantly ventilated cats. In one group, the peripheral arterial chemoreceptors remained innervated, whereas in the other they were denervated by bilateral cervical vagotomy and section of the carotid sinus nerves. 2. Animals with innervated chemoreceptors (n = 16) reacted to almitrine bismesylate with a significant (P <0.05) increase in both ACTH and cortisol. These responses were not present in cats in which the peripheral arterial chemoreceptors had been surgically denervated (n = 16). 3. Plasma renin activity and plasma aldosterone increased with time during experiments on both the chemoreceptor-intact and chemoreceptor-denervated cats. Almitrine did not affect the time course of the rise in PRA and plasma aldosterone in either group of animals. 4. These data indicate that, under the conditions of our experiments, almitrine induced arterial chemoreceptor reflex mechanisms stimulate ACTH and cortisol release, but has no chemoreceptor-dependent influence on PRA or plasma aldosterone.

Prolonged hemodynamic effects of intermittent, brief chemoreceptor stimulation in humans.

Augmented arterial chemoreceptor reflex tonic drive was observed in human subjects with essential mild hypertension and it was suggested as a sympatho-excitatory mechanism contributing to elevated blood pressure (Trzebski et al, 1982; Trzebski, 1992). Human subjects are exposed to repetitive episodic nocturnal hypoxic chemoreceptor stimulation in obturative sleep apnea syndrome (OSAS). In agreement with the original hypothesis on the role of the chemoreceptor reflex in hypertension, OSAS is usually accompanied by systemic arterial hypertension (Jeong et al, 1989; Hla et al, 1994) which is reversed by tracheostomy (Guilleminault et al, 1981). Repetitive, brief hypoxia produces in rats a sustained blood pressure elevation (Fletcher et al, 1992a) prevented by carotid chemoreceptor or sympathetic denervation (Fletcher et al, 1992b,c). In contrast to baroreceptors, chemoreceptors do not exhibit adaptation with long-lasting stimulation. On the contrary, their responsiveness appears to be enhanced with prolonged hypoxia (Smith et al, 1986; Barnard et al, 1987; Vizek et al, 1987; Nielsen et al, 1988; but Tatsumi, 1991). In awake OSAS patients resting sympathetic vasoconstrictor activity is augmented (Carlson et al, 1993). Morgan et al (1995) found long-lasting vasoconstrictor sympathetic activation in healthy human subjects after termination of a 20 min period of combined hypoxia and hypercapnia.KeywordsObstructive Sleep ApneaObstructive Sleep Apnea SyndromeCarotid BodyTotal Peripheral ResistanceSympathetic DenervationThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Hypothalamic modulation of the arterial chemoreceptor reflex in the anaesthetized cat: role of the nucleus tractus solitarii.

1. There is evidence in the literature of a mutual facilitatory interaction between the arterial chemoreceptor reflex and the alerting stage of the defence reaction, particularly in relation to the patterning of cardiorespiratory activity. The present study has been designed to test the hypothesis that a portion of this interaction involves synaptic interactions within the nucleus tractus solitarii (NTS). 2. The study has involved an analysis of the effective interactions between the stimulation of the arterial chemoreceptors and the hypothalamic defence area (HDA) on the activity of NTS neurones recorded in anaesthetized, paralysed and artificially ventilated cats. 3. A group of eighteen NTS neurones was classified as chemosensitive, on the basis of displaying EPSPs on sinus nerve stimulation (SN) and their failure to show an excitatory response to baroreceptor stimulation. Thirteen of these neurones displayed pronounced excitatory responses to chemoreceptor stimulation. In sixteen of these neurones HDA stimulation elicited an EPSP; in four of these sixteen neurones this early EPSP was followed by an IPSP. In the remaining two (of 18) neurones HDA stimulation provoked no obvious synaptic response but facilitated the efficacy of both chemoreceptor inputs and SN stimulation. 4. Neurones shown to receive convergent inputs from the arterial chemoreceptors (and SN stimulation) and HDA, often displayed excitatory responses to stimulation of other peripheral inputs. Vagally evoked EPSPs were observed in nine neurones, SLN-evoked responses in seven neurones and aortic nerve-evoked EPSPs in three neurones. 5. The organization of these synaptic interactions is discussed and these data are used to explain the pattern of interaction between chemoreceptor, baroreceptor and HDA inputs within the NTS. Conclusions are drawn regarding the functional role of different classes of NTS neurone, based on the findings in this and the accompanying two papers.

Cardiorespiratory responses to acute hypoxia and hyperoxia in adult and neonatal spontaneously hypertensive and normotensive rats.

The aim of this study was to investigate whether there are differences between particular characteristics of breathing regulation in primary hypertensive and normotensive states which might indicate significant differences in arterial chemoreceptor reflex function. Under air-breathing conditions, minute ventilation was similar in adult spontaneously hypertensive rats (SHR) (50 +/- 2ml/min x 100 g) and in Wistar-Kyoto rats (WKY) (54 +/- 3 ml/min x 100 g) but significantly lower in randomly bred normotensive Wistar rats (NWR) (39 +/- 1 ml/min x 100 g). In seven-day-old rats minute ventilation was 10.5 +/- 1.2ml/min x 10 g in SHR and 10.2 +/- 1.4 ml/min x 10 g in WKY. Our data indicate that there is no elevation of the ventilatory drive under air-breathing conditions which can be unequivocally associated with primary hypertension in adult and neonatal animals. Acute inhibition of ventilation caused by hyperoxia indicated that oxygen dependent peripheral chemoreceptor activity during air-breathing was similar in SHR and normotensive controls both in the unanesthetized neonatal state and in anesthetized adult animals. No well defined association between the characteristics of the hypoxic ventilatory response and primary hypertension could be demonstrated although responses in adult anesthetized SHR tended to be faster and of higher amplitude than in normotensive controls.

Role of the central and arterial chemoreceptors in the response of gastric tone and motility to hypoxia, hypercapnia and hypocapnia in rats

The contribution of autonomic nerve activity to stomach tone and motility during central and arterial chemoreceptor excitation or inhibition was analyzed in urethane anesthetized, artificially ventilated rats. Systemic severe hypoxia at end-tidal O 2 concentration ( F et O 2 ) 6% and systemic hypercapnia at end-tidal CO 2 concentration ( F et CO 2 ) 6%, 8% and 10% applied for 1 min produced a significant depression in gastric tone and motility. Hypocapnia at 3% F et CO 2 increased gastric tone and motility. Hypoxia co-activated both the sympathetic and the vagal efferent gastric nerve branches. Hypercapnia augmented only sympathetic gastric efferent nerve activity but not vagal efferent nerve activity. Hypocapnia slightly increased vagal nerve activity to the stomach. Bilateral denervation of the arterial chemoreceptors significantly attenuated the inhibitory gastric response to hypoxia. Similar attenuation of hypoxia-induced depression of gastric tone and motility was produced by bilateral gastric sympathectomy but not by vagotomy. In contrast, the inhibitory effect of severe hypercapnia and the facilitatory effect of hypocapnia upon gastric tone and motility were unaffected by arterial chemoreceptor denervation, by severance of gastric sympathetic branches or by gastric vagal denervation. Hyperoxia at 90% F et O 2 had no effect on the gastric nerve activities, gastric tone or motility. It is concluded that in the rat hypoxia co-activates sympathetic and vagal efferent nerve activities to the stomach via an arterial chemoreceptor reflex, and that hypercapnia activates sympathetic gastric nerve activity via central chemoreceptors. Hypocapnia activates efferent vagal gastric nerve activity. All chemical stimuli except that of hyperoxia have a significant local effect on the gastric tone and motility. Hypoxia-induced depression depends on the contribution of activated gastric sympathetic nerves via arterial chemoreceptors. Stimulatory effects of hypocapnia are mainly local, with no significant contribution of the arterial or central chemoreceptors. Results obtained by applying severe hypercapnia do not provide evidence that arterial and central chemoreceptors contribute significantly to inhibition of gastric tone and motility by stimulation of gastric sympathetic nerve activity.

Inhibition of arterial baroreceptor and chemoreceptor reflex responses by neuropeptide Y in anaesthetised dogs

The effects of bolus intravenous injections of neuropeptide Y (NPY) on increases in pulse interval (PI) evoked reflexly by arterial chemoreceptor and baroreceptor stimulation were investigated in anaesthetised dogs. The arterial chemoreceptors were stimulated by rapid injections of small volumes of CO 2 into the carotid sinus or brief episodes of tracheal occlusion. Intravenous injections of NPY produced a prolonged attenuation of the reflex prolongation of PI induced by both methods. Two methods of testing the arterial baroreceptor reflex were used: steady-state increases in PI evoked in response to maintained step increases in systolic arterial blood pressure (SABP) from inflation of an aortic balloon-tipped catheter, and beat-by-beat increases in PI evoked reflexly by ‘ramp’ increases in blood pressure caused by intravenous injections of phenylephrine. In both methods the relationship between SABP and PI is linear over the range tested (up to SABP 200 mmHg), the slope of the line indicating the sensitivity of the reflex response. Intravenous injections of NPY produced a prolonged attenuation of the baroreceptor-cardiodepressor reflex measured by both methods. No significant differences were observed between the NPY-mediated inhibition of the direct effects on PI of electrical stimulation of a vagus nerve, and its inhibition of the reflex responses of PI to chemoreceptor or baroreceptor stimulation. The results indicate that the attenuation of reflex PI responses to arterial chemoreceptor and baroreceptor stimulation following an intravenous injection of NPY can be accounted for in terms of the action of NPY on vagal nerve endings at the heart, although additional sites of action cannot be ruled out.

Peripheral arterial chemoreceptors and reflex control of sodium and water homeostasis

In response to acute exposure to moderate high-altitude hypoxia, mammals increase their blood hemoglobin concentration very rapidly by reducing their plasma volume. This phenomenon is caused not only by a redistribution of the body fluid volumes but also by a suppression of voluntary sodium and water intake as well as an inhibition of renal tubular sodium reabsorption with natriuresis and diuresis. This article reviews the role of the peripheral arterial chemoreceptors within the framework of the reflex mechanisms that might cause the changes in sodium and water metabolism in acute arterial hypoxia. The evidence that the peripheral arterial chemoreceptors do also influence sodium and water homeostasis in normoxia is presented. The interrelations between carotid body structure and arterial chemoreceptor reflex effects on the one hand and primary systemic hypertension on the other are discussed.

Chemoreceptor stimulation interferes with regional hypoxic pulmonary vasoconstriction

Hypoxemia interferes with the diversion of blood flow away from hypoxic regions of the lung, possibly through activation of the arterial chemoreceptor reflex. The purpose of this study was to determine if selective stimulation of carotid chemoreceptors reduces the diversion of flow (hypoxic vasoconstriction) when normal systemic oxygen levels are present. Chloralose anesthetized dogs were paralyzed and each lung was separately ventilated via a dual-lumen endobronchial tube. left pulmonary artery (Q̇L) and main pulmonary artery (Q̇T) blood flows were measured with electromagnetic flow probes. Chemoreceptors were stimulated by perfusion of the carotid sinuses with hypoxic, hypercapnic blood. Q̇L/Q̇T averaged 46±4, 29±2, and 36±4% during bilateral O 2 ventilation (control), left lung N 2 ventilation, and left lung N 2 plus chemoreceptor stimulation in dogs treated with the cyclo-oxygenase inhibitor meclofenamate. After vagotomy, Q̇L/Q̇T averaged 45±4, 27±3, and 28±2% during the same conditions. Q̇L/Q̇T decreased significantly from control ( P < 0.05) during left lung N 2 alone but did not decrease during left lung N 2 plus chemoreceptor stimulation in dogs with intact vagi. In contrast, Q̇L/Q̇T decreased significantly both before and during chemoreceptor stimulation in vagotomized dogs. The same responses were observed in dogs not treated with meclofenamate. These results indicate that selecitive stimulation of arterial chemoreceptors can interfere with regional hypoxic vasoconstriction and suggest that the vagus nerves may mediate this effect.

Split medulla preparation in the cat: arterial chemoreceptor reflex and respiratory modulation of the renal sympathetic nerve activity

The study was undertaken in order to assess the changes in sympathetic output in a split medulla preparation of the cat which, as shown earlier, has impaired respiratory rhythm generation. The effects of medullary midsagittal sections on renal sympathetic nerve firing were investigated in chloralose anesthetized, paralyzed and artificially ventilated cats. Recordings of phrenic and recurrent laryngeal nerve activity served as indices of central respiratory rhythm generation. Sections, 5 mm deep from the dorsal medullary surface and extending 6 mm rostrally and 3 mm caudally to the obex, did not produce any significant changes in heart rate, blood pressure or tonic renal sympathetic nerve firing levels. They decreased or abolished, however, the respiratory rhythmicity in renal sympathetic nerve which paralleled the reduction of inspiratory discharges in phrenic and recurrent laryngeal nerves, and abolished the carotid body chemoreceptor-sympathetic reflex. The inspiratory activity remaining after the sections could still be enhanced by chemoreceptor stimulation. The inhibitory baroreceptor and pulmonary stretch receptor sympathetic reflexes, and the central excitatory effect of CO 2 on renal sympathetic nerve firing were not altered. The effects of electrical stimulation within the midsagittal plane of the medulla have shown that descending pathways from the medullary inspiratory neurons (or their medullary collaterals) do not participate in the facilitation of spinal preganglionic neurons during inspiration and in relaying the pulmonary stretch receptor inhibitory sympathetic reflex. A region located close to the obex was identified from which excitatory responses in renal sympathetic nerves, compatible with the response obtained by carotid sinus nerve stimulation, could be evoked. It is concluded that a lesion in the midline of the lower medulla at the level of the obex selectively destroys cells or pathways which relay the carotid body chemoreceptor-sympathetic reflex.

Rapid cerebral vasodilatation in brief hypoxia in anaesthetized animals.

In anaesthetized dogs, cats and rabbits, intracranial pressure was measured continuously during brief or transient hypoxia, induced by (a) lowering inspired O2 to 9--10% for 2--3 min, or (b) giving 2--3 breaths of nitrogen. In almost all instances there was an increase in i.c.p. which started in less than 20 s; this occurred with either spontaneous or controlled ventilation, and whether or not there was also a rise in arterial blood pressure; the time course was similar to that of the arterial chemoreceptor reflex responses of ventilation and blood pressure. Division bilaterally of the sinus and vagus nerves in six cats showed that the intracranial pressure response was not dependent on these chemoreceptor afferent pathways. The results suggest a rapid vasodilatation starting at a time when cerebral arterial oxygen tension is unlikely to be below 7 kPa (50 mmHg). The mechanism remains unexplained.

Influence of CO2 on cardiovascular response to hypoxia in conscious dogs.

The modulating effect of CO2 on the circulatory response to hypoxia in chronically instrumented conscious dogs was examined over a wide range of arterial partial pressure of O2 [PaO2 (from 80 to 25 Torr)] during a 41-min rebreathing period at three CO2 levels: hypocapnia (from PaCO2 of 32 to 18 Torr), eucapnia (32 Torr), and mild hypercapnia (40 Torr). Eucapnic and hypercapnic hypoxic responses were also measured after sinoaortic denervation (SAD) to assess the arterial chemoreceptor and baroreceptor reflex contributions. Elevating PaCO2 attenuated the tachycardia during hypoxia and produced progressively greater systemic, renal, and splanchnic vasoconstriction before but not after SAD. Vagal block converted the rises in renal and splanchnic flows observed during hypocapnic hypoxia to declines. The increase in left ventricular dP/dtmax was not affected by varying PaCO2 either before or after SAD. Coronary flow increased an additional onefold during hypoxia when PaCO2 was elevated both before and after SAD, but the tension-time indices did not differ significantly. These results indicate that: a) cardiopulmonary vagal afferents effectively counteract chemoreflex-induced vasoconstriction during hypocapnic hypoxia; b) chemoreflex vasoconstriction predominates in the renal and splanchnic beds when PaCO2 is elevated; c) the sinoaortic reflexes restrain the heart rate, but not the contractility response to hypoxia when PaCO2 is increased; and d) the augmented coronary vasodilation produced by CO2 is probably mediated by local CO2-hypoxic interactions.

Depression of ventilation by dopamine in man. Evidence for an effect on the chemoreceptor reflex.

Dopamine is present in the carotid body and has been postulated to be an inhibitory neurotransmitter. The purpose of this study was to determine the effects of dopamine on ventilation in man and to examine its mechanism of action. Dopamine (0.5-10 mug/kg per min) was infused in eight normal men at different levels of arterial chemoreceptor activity, produced by varying the inspired Po(2). During normoxia dopamine produced a small decrease in minute ventilation (Ve) and an increase in arterial Pco(2). When arterial chemoreceptors were stimulated by hypoxia, infusion of dopamine produced a marked initial depression of Ve followed by a sustained although less pronounced decrease in Ve. An increase in Pa(co) (2) and a decrease in Pao(2) were also observed. When arterial chemoreceptor activity was suppressed by hyperoxia, infusion of dopamine did not affect ventilation. Subjects also breathed a hypercarbic, hyperoxic gas mixture. The hypercarbia produces hyperventilation by stimulating central chemoreceptors, whereas the hyperoxia suppresses peripheral chemoreceptors. Dopamine did not alter ventilation while the subjects were breathing this gas mixture. These studies suggest that dopamine suppresses ventilation in man through an action on the arterial chemoreceptor reflex. These findings support the hypothesis that dopamine is an inhibitory neurotransmitter in the carotid body, and that release of dopamine may modulate the sensitivity of peripheral arterial chemoreceptors.