Afferent properties and reflex functions of bronchopulmonary C-fibers.

Bronchopulmonary C-fiber afferents are characterized by their distinct sensitivity to chemical stimuli in the airways or pulmonary circulation. Responses evoked by activating these afferents are mediated by both central reflex pathways and by local or axon reflexes involving the release of tachykinins from sensory endings. Bronchopulmonary C-fiber stimulation reflexly reduces tidal volume and increases respiratory rate, constricts the airways, increases mucus secretion in the airways, and is associated with coughing. Cardiovascular effects include bradycardia, a fall in cardiac output, and bronchial vasodilation that increases airway blood flow despite systemic hypotension. In animals, C-fiber stimulation inhibits skeletal muscle activity, and in humans, is accompanied by burning and choking sensations in the throat and upper chest. Recent studies have identified additional physiologic and pharmacologic stimuli to these afferents, such as hydrogen ions, adenosine, reactive oxygen species, and hyperosmotic solutions. Furthermore, increasing evidence indicates that the excitability of these afferents is enhanced by the local release of certain autocoids (e.g. PGE2) during airway inflammation. These findings further indicate that vagal C-fiber endings in the lungs and airways play an important role in regulating the cardiopulmonary functions under both normal and abnormal physiologic conditions.

Bronchial vasodilation evoked by increased lower airway osmolarity in dogs.

Hyperosmotic saline solutions stimulate lower airway sensory nerves. To determine whether airway hyperosmolarity evokes neurally mediated changes in bronchial artery blood flow (Qbr), we measured the effect of injection of small volumes (1 ml) of hyperosmotic saline into a right lobar bronchus on Qbr of anesthetized, artificially ventilated dogs. In 14 dogs, hyperosmotic saline (1,200 and 2,400 mmol/l) increased Qbr by 58 +/- 12 (SE) and 118 +/- 12%, respectively, from a baseline of 8 +/- 2 ml/min. Qbr increased within 6-8 s of the injections, peaked at 20 s, and returned to control over 2-3 min. Isosmotic saline had minimal effects. In contrast, hyperosmotic saline decreased flow in an intercostal artery that did not supply the airways. The bronchial vasodilation was decreased by 72 +/- 11% after combined blockade of alpha-adrenoceptors and muscarinic cholinergic receptors and by 66 +/- 6% when the cervical vagus nerves were cooled to 0 degrees C. Blockade of H(1) and H(2) histamine receptors did not reduce the nonvagal response. We conclude that hyperosmolarity of the lower airways evokes bronchial vasodilation by both a centrally mediated reflex that includes cholinergic and adrenergic efferent pathways and by unidentified local mechanisms.

Bronchial vasodilator pathways in the vagus nerve of dogs.

Bronchial vasodilation in dogs is mediated largely by vagal pathways. To examine the relative contribution of cholinergic and noncholinergic parasympathetic pathways and of sensory axon reflexes to vagal bronchial vasodilation, we electrically stimulated the peripheral vagus nerve in 10 chloralose-anesthetized dogs and measured bronchial artery flow. Moderate-intensity electrical stimulation (which did not activate C-fiber axons) caused a rapid voltage- and frequency-dependent vasodilation. After atropine, vasodilation was slower in onset and reduced at all voltages and frequencies: bronchial vascular conductance increased by 9.0 +/- 1.5 (SE) ml. min-1. 100 mmHg-1 during stimulation before atropine and 5. 5 +/- 1.4 ml. min-1. 100 mmHg-1 after (P < 0.02). High-intensity stimulation (sufficient to recruit C fibers) was not studied before atropine because of the resulting cardiac arrest. After atropine, high-intensity stimulation increased conductance by 12.0 +/- 2.5 ml. min-1. 100 mmHg-1. Subsequent blockade of ganglionic transmission, with arterial blood pressure maintained by a pressure reservoir, abolished the response to moderate-intensity stimulation and reduced the increase to high-intensity stimulation by 82 +/- 5% (P < 0.01). In 13 other dogs, we measured vasoactive intestinal peptide-like immunoreactivity in venous blood draining from the bronchial veins. High-intensity vagal stimulation increased vasoactive intestinal peptide concentration from 5.7 +/- 1.8 to 18.4 +/- 4.1 fmol/ml (P = 0.001). The results suggest that in dogs cholinergic and noncholinergic parasympathetic pathways play the major role in vagal bronchial vasodilation.

Reflex tracheal smooth muscle contraction and bronchial vasodilation evoked by airway cooling in dogs.

Cooling intrathoracic airways by filling the pulmonary circulation with cold blood alters pulmonary mechanoreceptor discharge. To determine whether this initiates reflex changes that could contribute to airway obstruction, we measured changes in tracheal smooth muscle tension and bronchial arterial flow evoked by cooling. In nine chloralose-anesthetized open-chest dogs, the right pulmonary artery was cannulated and perfused; the left lung, ventilated separately, provided gas exchange. With the right lung phasically ventilated, filling the right pulmonary circulation with 5 degrees C blood increased smooth muscle tension in an innervated upper tracheal segment by 23 +/- 6 (SE) g from a baseline of 75 g. Contraction began within 10 s of injection and was maximal at approximately 30s. The response was abolished by cervical vagotomy. Bronchial arterial flow increased from 8 +/- 1 to 13 +/- 2 ml/min, with little effect on arterial blood pressure. The time course was similar to that of the tracheal response. This response was greatly attenuated after cervical vagotomy. Blood at 20 degrees C also increased tracheal smooth muscle tension and bronchial flow, whereas 37 degrees C blood had little effect. The results suggested that alteration of airway mechanoreceptor discharge by cooling can initiate reflexes that contribute to airway obstruction.

Reflex bronchial vasodilation in dogs evoked by injection of a small volume of water into a bronchus.

Injection of water into a lobar bronchus stimulates airway C-fibers and rapidly adapting receptors and evokes airway defense reflexes. To determine whether this stimulus also evokes a reflex increase in bronchial blood flow (Qbr), we injected 1-2 ml of water into a lobar bronchus in anesthetized dogs. Injection decreased arterial pressure but increased Qbr from 9 +/- 1 to 21 +/- 3 ml/min. The increase had a latency of 6-8 s and reached a peak after approximately 20 s; Qbr returned to control after 60-90 s. Airway mucosal blood flow, measured by colored microspheres, increased in proportion to Qbr. In contrast, flow in an adjacent intercostal artery that did not supply the airway decreased slightly. Injection of isosmotic saline had little effect. In 13 of 16 dogs, the water-induced increase in Qbr was abolished by cutting or cooling the cervical vagus nerves and hence was entirely dependent on centrally mediated vagal pathways. When the vagus nerves were intact, about one-third of the vasodilator response remained after pharmacological blockade of muscarinic and adrenergic receptors. We conclude that in dogs the defense response to water in the lower airways includes a large increase in Qbr that is partly due to activation of nonadrenergic noncholinergic autonomic pathways.

Cooling the pulmonary blood in dogs alters activity of pulmonary vagal afferents.

In open-chest anesthetized dogs with left and right lungs ventilated separately, we recorded changes in firing of right lung vagal receptors when 1.25 ml/kg cold (5 degrees C, 20 degrees C) blood were injected into the nonperfused right pulmonary artery. With the right lung inflated at constant pressure, effects of cold blood on individual pulmonary stretch receptors (PSRs) were frequency dependent, with discharge increasing or remaining unchanged if control frequency was low and decreasing if it was high. Consequently average PSR discharge was unchanged by cold blood when airway pressure was maintained at 5 cmH2O, but it decreased at pressures of 10 and 15 cmH2O. Cold blood stimulated rapidly adapting receptors (RARs) at all three pressures. Injection of blood at 37 degrees C had no effect. We conclude that changes in PSR activity account for the tachypnea induced by pulmonary arterial injection of cold blood (G. G. Giesbrecht and M. Younes. J. Appl. Physiol. 69: 1435-1441, 1990). With the right lung phasically ventilated, cold blood decreased PSR discharge in inflation, caused high-threshold PSRs to fire in deflation, and stimulated RARs. Pulmonary C-fibers were unaffected by cold blood. We suggest that PSRs and RARs initiate respiratory changes during hypothermia or exercise-induced asthma.

Capsaicin-induced bronchial vasodilation in dogs: central and peripheral neural mechanisms.

In 21 anesthetized dogs, we placed a flow probe around the right bronchial artery and examined changes in bronchial blood flow and bronchial vascular conductance when pulmonary C-fibers were stimulated by right atrial injection of capsaicin. When vagus nerves were intact, capsaicin evoked a pulmonary depressor chemoreflex and increased bronchial blood flow by 125% and bronchial vascular conductance by 175%; flow in an adjacent intercostal artery did not increase. Injection of color-coded microspheres revealed that blood flow to mucosa of lower trachea and to a peripheral bronchus doubled, whereas flow to posterior tracheal wall increased little. Cooling (to -1 degree C) or cutting cervical vagi (in 17 dogs) abolished the pulmonary chemoreflex and abolished all bronchial vascular effects in nine dogs but 33% of the vasodilation persisted in eight. In five of six dogs, this persisting vasodilation was potentiated by phosphoramidon (a neutral endopeptidase inhibitor that retards breakdown of neuropeptides released by C-fibers). Atropine reduced the capsaicin-induced bronchial vasodilation by approximately 30%. We conclude that the bronchial vasodilation was largely due to a centrally mediated vagal reflex and that a neuropeptide-dependent axon-reflex component was also present in about one-half the dogs.

Vagal afferent and reflex responses to changes in surface osmolarity in lower airways of dogs.

In anesthetized dogs we examined the sensitivity of afferent vagal endings in the lungs to changes in airway fluid osmolarity. Injection of 0.25-0.5 ml/kg water or hyperosmotic sodium chloride solutions (1,200-2,400 mmol/l) into a lobar bronchus caused bradycardia, arterial hypotension, apnea followed by rapid shallow breathing, and contraction of tracheal smooth muscle. All effects were abolished by vagotomy. We examined the sensory mechanisms initiating these effects by recording afferent vagal impulses arising from the lung lobe into which the liquids were injected. Water stimulated pulmonary and bronchial C-fibers and rapidly adapting receptors; isosmotic saline and glucose solutions were ineffective. Hyperosmotic saline (1,200-9,600 mmol/l, 0.25-1 ml/kg) stimulated these afferents in a concentration-dependent manner. Stimulation began 1-10 s after the injection and sometimes continued for several minutes. Responses of slowly adapting stretch receptors varied. Our results suggest that non-isosmotic fluid in the lower airways initiates defense reflexes by stimulating pulmonary and bronchial C-fibers and rapidly adapting receptors. Conceivably, stimulation of these afferents as a result of evaporative water loss from airway surface liquid could contribute to exercise-induced asthma.

Response of slowly adapting pulmonary stretch receptors to reduced lung compliance.

We examined the steady-state response of slowly adapting pulmonary stretch receptors (SAPSRs) to reduced lung compliance in open-chest cats with lungs ventilated at eupneic rate and tidal volume (VT) and with a positive end-expiratory pressure (PEEP) of 3-4 cmH2O. Transient removal of PEEP decreased compliance by approximately 30% and increased transpulmonary pressure (Ptp) by 1-2.5 cmH2O. Reduction of compliance significantly decreased SAPSR discharge in deflation and caused a small increase in discharge at the peak of inflation; it had little effect on discharge averaged over the ventilatory cycle. Increasing VT to produce a comparable increase in Ptp significantly increased peak discharge. Thus unlike rapidly adapting receptors, whose discharge is increased more effectively by reduced compliance than by increased VT, SAPSRs are stimulated by increased VT but not by reduced compliance. We speculate that the most consistent effect of reduced compliance on SAPSRs (the decrease in deflation discharge) was due to the decreased time constant for deflation in the stiffer lung. This alteration in firing may contribute to the tachypnea evoked as the lungs become stiffer.

Intravenous injection of hypertonic NaCl solution stimulates pulmonary C-fibers in dogs.

Intravenous injection of hypertonic NaCl solution evokes reflex bradycardia and hypotension, effects thought to result from stimulation of afferent vagal endings in the lungs. To identify the afferents responsible for these effects, we recorded vagal impulses arising from endings in the lungs and lower airways of anesthetized dogs and examined the response to injection of hypertonic solutions into the pulmonary circulation. Injection of 4,800 mmol/l NaCl solution (1 ml/kg) stimulated 39 of 49 pulmonary C-fibers, their impulse frequency increasing 35-fold. Stimulation was concentration dependent, the minimum effective concentration being between 1,200 and 4,800 mmol/l. Rapidly adapting receptors were also stimulated in a concentration-dependent manner, 35 of 41 receptors being stimulated by 4,800 mmol/l NaCl solution, firing increasing fivefold. Bronchial C-fibers were not stimulated by injection into the pulmonary circulation but were by injection into the bronchial artery. Hypertonic urea solutions had qualitatively similar but smaller effects on pulmonary C-fibers and rapidly adapting receptors. The results suggest that the reflex effects of intravenous injection of hypertonic solutions result principally from stimulation of pulmonary C-fibers.

Reflex coronary vasodilation evoked by chemical stimulation of cardiac afferent vagal C fibres in dogs.

1. Veratridine injected into the coronary circulation stimulates afferent vagal endings in the heart to evoke bradycardia and systemic hypotension (Bezold-Jarisch reflex, coronary chemoreflex) and coronary vasodilation. We have examined certain features of the reflex coronary vasodilator response in anaesthetized dogs. 2. When the circumflex coronary artery was perfused at constant pressure (100 mmHg), injection of veratridine (0.3 micrograms kg-1) into the anterior descending artery decreased blood pressure and heart rate, and increased circumflex blood flow by 54%; when heart rate was kept constant, circumflex flow increased by 57%. The increase in circumflex flow was reduced 63% by atropine, and finally abolished by phentolamine. 3. During severe coronary underperfusion (perfusion pressure 45 mmHg), veratridine still increased coronary flow by 35%, an increase amounting to 24-64% of the coronary vascular reserve. Flow increased in all layers of the myocardium, but the relative distribution of flow between subendocardial and subepicardial layers was unaltered. 4. Veratridine stimulates both mechanosensitive and chemosensitive cardiac endings. Stimulating chemosensitive afferents selectively by injecting capsaicin (1.5 micrograms kg-1) into the anterior descending artery decreased blood pressure and heart rate, and increased circumflex flow by 50% (and by 36% when heart rate was kept constant). 5. In ten of fifteen dogs, veratridine and capsaicin still evoked coronary vasodilatation when vagal A fibres were blocked selectively by cooling to 7.5 degrees C, the increase in coronary flow averaging 45% of that at 37 degrees C. All responses were abolished by cooling to 0 degrees C. 6. We conclude that coronary vasodilatation can be evoked by selective stimulation of cardiac chemosensitive vagal C fibres, although the coronary vasodilation of the veratridine-induced Bezold-Jarisch reflex may be due to stimulation of both mechanosensitive and chemosensitive C fibres. We speculate that during periods of coronary underperfusion ischaemic stimulation of chemosensitive vagal C fibres evokes a reflex dilatation of the coronary vascular bed that supplements the dilatation dependent upon autoregulatory mechanisms.

Rapidly adapting receptors monitor lung compliance in spontaneously breathing dogs.

We examined the ability of rapidly adapting receptors (RARs) to monitor changes in dynamic lung compliance (Cdyn) in anesthetized spontaneously breathing dogs by recording RAR impulses from the vagus nerves. We decreased Cdyn in steps through the physiological range by briefly restricting lung expansion with an inflatable cuff around the chest and recording the response after deflating the cuff; we restored Cdyn to control by hyperinflating the lungs. Of 45 RARs, 34 were stimulated by a 40 +/- 2% reduction in Cdyn, their inspiratory discharge increasing on average more than threefold. Two-thirds of responsive RARs were stimulated by less than or equal to 20% reductions in Cdyn; in most, firing increased proportionately with lung stiffness (1/Cdyn) as Cdyn was decreased further. Stimulation by reduced Cdyn was not simply a function of the concomitant increase in transpulmonary pressure, because similar increases in pressure produced by increasing tidal volume produced smaller increases in firing. RAR stimulation was unaffected by atropine and, hence, was not dependent on neurally mediated changes in bronchomotor tone. Our results indicate that during spontaneous breathing RARs provide a signal inversely proportional to Cdyn.

Usefulness and limitations of regional cardiac sympathectomy by phenol.

We evaluated the completeness and extent of regional sympathetic denervation of the left ventricle after epicardial painting with phenol in anesthetized dogs. In a region encircled by phenol, the effect of electrical stimulation of efferent sympathetic fibers on myocardial contractility and coronary vascular resistance was completely abolished within 30 min. Denervation extended to untreated regions innervated by sympathetic fibers crossing the phenol line. For at least 4 h after phenol application, intravenous infusion of isoproterenol or coronary arterial infusion of tyramine increased myocardial contractility in the denervated region; norepinephrine content and neurotransmitter uptake were normal, indicating that nerve terminals, postjunctional receptors, and myocardium remained functional. However, after 3-14 days, tissue catecholamine content and transmitter uptake in the encircled area were markedly reduced. The results suggest that careful evaluation is necessary in selecting a fully innervated control region in studies employing regional sympathetic denervation with phenol.

Stimulation of vagal pulmonary C-fibers by a single breath of cigarette smoke in dogs.

Inhalation of cigarette smoke into the lower airway via a tracheostomy evokes immediate apnea, bradycardia, and systemic hypotension in dogs. These responses can still be evoked when conduction in myelinated vagal fibers is blocked preferentially by cooling but are abolished by vagotomy, suggesting that they are mediated by afferent vagal C-fibers. To examine this possibility, we recorded impulses in pulmonary C-fibers in anesthetized, open-chest dogs and delivered 120 ml cigarette smoke to the lungs in a single ventilatory cycle. Pulmonary C-fibers were stimulated within 1 or 2 s of the delivery of smoke generated by high-nicotine cigarettes, activity increasing from 0.3 +/- 0.1 to a peak of 12.6 +/- 1.3 (SE) impulses/s, (n = 60); the evoked discharge usually lasted 3-5 s. Smoke generated by low-nicotine cigarettes evoked a milder stimulation in 33% of pulmonary C-fibers but did not significantly affect the overall firing frequency (peak activity = 2.2 +/- 1.1 impulses/s, n = 36). Hexamethonium (0.7-1.2 mg/kg iv) prevented C-fiber stimulation by high-nicotine cigarette smoke (n = 12) but not stimulation by right atrial injection of capsaicin. We conclude that pulmonary C-fibers are stimulated by a single breath of cigarette smoke and that nicotine is the constituent responsible.

Attenuation of pulmonary afferent input by vagal cooling in dogs.

In open chest, artificially ventilated, anesthetized dogs, we examined the effect of vagal cooling on the pulmonary afferent input evoked by hyperinflating the lungs to 3 VT, recording the activity of slowly adapting pulmonary stretch receptors (PSRs), rapidly adapting receptors (RARs) and pulmonary C fibers rostral to the cooling platform. At 15 degrees C and below, input in all three types of fiber was significantly reduced, attenuation being least marked in C fibers. Between 12 degrees C and 7 degrees C, attenuation of RAR input was significantly less than that of PSRs. At 7 degrees C, virtually none of the hyperinflation-evoked increase in PSR activity and only 10% of that in RARs passed the cooling platform--indeed RAR input was less than during normal ventilation at 37 degrees C; by contrast, 40% of the hyperinflation-evoked increase in C fiber activity was still transmitted. Cooling had similar effects on C fiber input evoked by capsaicin. If reflexes are attenuated in proportion to the attenuation of afferent input, our results suggest that a hyperinflation-evoked reflex that survives vagal cooling below 6 degrees C is almost certainly triggered by C fibers.

Carotid sinus baroreceptors modulate tracheal smooth muscle tension in dogs.

Arterial baroreceptors are known to influence airway smooth muscle tone. Thus, increasing carotid sinus pressure from 20 to 200 mm Hg causes reflex tracheal dilation. However, the effects of changing sinus pressure around a normal arterial pressure set-point of 100 mm Hg have not been examined. In anesthetized, artificially ventilated dogs, we distended the vascularly isolated carotid sinuses with a pulsatile pressure and recorded isometric tension in an upper tracheal segment. The aortic nerves were cut. Increasing mean carotid sinus pressure in steps between 100 and 200 mm Hg decreased tracheal tension, heart rate, and arterial blood pressure; decreasing sinus pressure between 100 and 25 mm Hg had the opposite effect. Changing carotid sinus pressure still evoked tracheal responses when systemic arterial pressure was held constant. Increasing and decreasing carotid sinus pulse pressure around a constant mean pressure evoked similar changes in tracheal tension. All reflex effects were abolished by cutting or cooling (0 degree C) the carotid sinus nerves; tracheal responses were abolished by the carotid baroreflex were of comparable magnitude to those triggered by stimulating pulmonary stretch receptors, laryngeal receptors, and pulmonary C-fibers. Our results indicate that carotid sinus baroreceptors exert a tonic influence on the upper airways by a vagal cholinergic pathway, increasing and decreasing tracheal smooth muscle tension as blood pressure varies around the normal set-point.

Rapidly adapting receptor activity in dogs is inversely related to lung compliance.

We examined the response of pulmonary rapidly adapting receptors (RAR's) to changes in dynamic lung compliance (Cdyn) in the physiological range. RAR impulse activity was recorded from the cervical vagus nerves in anesthetized open-chest dogs whose lungs were ventilated at constant rate and tidal volume (VT), with a positive end-expiratory pressure (PEEP) of 3-4 cmH2O. After hyperinflation to produce maximal Cdyn, RAR's were silent or fired sparsely and irregularly. Reducing Cdyn in steps by briefly removing PEEP increased firing proportionately, and RAR's began to discharge vigorously in inflation. Activity was restored to control by hyperinflating the lungs. Activity also increased when we increased inflation rate, and hence the rate of change of airway pressure (dP/dt), by reducing inflation time, keeping VT and cycle length constant. RAR's were stimulated more when dP/dt was increased by reducing compliance than when dP/dt was increased by increasing inflation rate. We conclude that RAR's are sensitive to changes in Cdyn and speculate that excitatory input from RAR's may help to maintain VT as the lungs become stiffer.

Background activity in pulmonary vagal C-fibers and its effects on breathing.

Vagal cooling experiments suggest that the deep slow breathing observed after vagotomy results not only from loss of pulmonary stretch receptor feedback, but also from loss of some unidentified vagal input. To investigate this possibility we cooled the vagus nerves in anesthetized dogs. In dogs breathing spontaneously, the Hering-Breuer reflex was abolished at 7 degrees C, but average expiratory time was unchanged and lengthened only on cooling below 3 degrees C. In artificially ventilated dogs the pulmonary vagus nerves were cooled in the chest and phrenic activity was recorded. Entrainment of phrenic bursts to the ventilator cycle ceased at 7 degrees C, and expiratory pauses shortened; they lengthened again on cooling below 3 degrees C. Cervical vagotomy did not change breathing pattern after the pulmonary vagus nerves were cut. Recording of afferent impulses during cooling showed that at 5 degrees C or less pulmonary vagal input was confined largely to nonmyelinated fibers; at 3 degrees C, background activity in pulmonary C-fibers was still 78% of control whereas myelinated afferents were virtually silent. We suggest that in eupnea low frequency, background activity in pulmonary afferent C-fibers shortens expiratory time.

Reduced effectiveness of the carotid baroreflex during arterial hypoxia in dogs.

The ability of the carotid baroreflex to produce cardiac slowing during arterial hypoxia was investigated in dogs anesthetized with morphine-chloralose. The heart rate response to baroreflex stimulation decreased by about 20% at an arterial O2 tension (PaO2) of 65-70 Torr and by over 60% at a PaO2 of 15-20 Torr. After the aortic nerves were cut bilaterally, baroreflex stimulation produced greater cardiac slowing (P less than 0.001) during arterial hypoxia (PaO2 20 Torr) than at the same PaO2 with intact aortic nerves. The systemic depressor response to baroreflex stimulation was reduced in a qualitatively similar manner but with greater variability. After atropine (0.2 mg/kg iv) or vagal transection the heart rate response to baroreflex stimulation during hypoxia was not suppressed from its control. Perfusion of the head with hypoxic blood in carotid-denervated animals also reduced the baroreflex bradycardia. The results suggest that the vagal component of the baroreflex bradycardia is suppressed during arterial hypoxia both by a reflex mediated by the aortic chemoreceptors and by a direct effect of hypoxia on the central nervous system.

Interaction between depressor and pressor reflexes arising from the aorta in dogs.

In 18 dogs anesthetized with morphine-chloralose the interaction between the aortic nerve (AN) pressor and depressor reflexes was studied. Low-intensity, high-frequency electrical stimulation of the AN causes large decreases in heart rate and systemic pressure characteristic of baroreflex responses. High-intensity, low-frequency stimulation of the AN causes modest increases in heart rate and systemic pressure similar to the responses observed to intraaortic nicotine. Simultaneous electrical stimulation of these antagonistic reflexes results in much smaller (P less than 0.001) reductions in heart rate and systemic pressure that can be explained on the basis of simple addition of the individual responses. Similarly the AN depressor reflexes are suppressed during intraaortic infusions of nicotine (40 micrograms/min). The results suggest that the inhibitory effects of the AN baroreflexes are suppressed by the aortic chemoreflexes . This interaction occurs in the CNS rather than at the level of the heart or vascular smooth muscle.