The effect of plasma volume expansion on the response to carotid occlusion in the non-human primate

The purpose of this study was to investigate the effects of plasma volume expansion on the cardiac and peripheral components of the baroreceptor reflex. Nine male Rhesus monkeys were chronically instrumented to measure arterial pressure and aortic blood flow. The aortic arch was denervated at the time of surgery. Bilateral carotid artery occlusion (BCO) was used to elicit the carotid sinus reflex both before and after 25% plasma volume expansion with an iso-osmotic dextran solution. The BCO elicited significant increases in heart rate (HR, 29.8 +/- 5.3 bpm) mean arterial pressure (MAP, 55.0 +/- 8.2 mm Hg) and total peripheral resistance (TPR, 0.076 +/- 0.01 mm Hg/ml/min) coupled with a significant reduction in mean aortic flow (AF, -246.9 +/- 55.3 ml/min) and stroke volume (SV, -2.86 +/- 0.36 ml). Volume expansion significantly attenuated the HR (15.2 +/- 5.8 bpm), MAP (30.4 +/- 4.4 mm Hg) and TPR (0.036 +/- 0.006 mm Hg/ml/min) response to carotid sinus hypotension. The changes in mean AF and SV elicited by BCO, however, were not significantly different between the control and volume expansion conditions. These data suggest that plasma volume expansion significantly attenuates the baroreceptor reflex control of circulation with a similar reduction in both the peripheral resistance and heart rate components of the response.     

Role of the solitary tract nucleus in mediating nociceptive evoked cardiorespiratory responses

We compared the cardiorespiratory reflex responses evoked by noxious stimulation of the forelimb and cornea. Due to the depressant effects of anaesthesia on visceral reflexes we compared data from an unanaesthetised decerebrate rat model--the working heart-brainstem preparation (WHBP), with the anaesthetised rat. In both experimental models stimulation of the forelimb (mechanical pinch) evoked a tachycardia (WHBP: 19 +/- 2 bpm) and a decrease in respiratory cycle length (WHBP: from 4.1 +/- 0.2 to 2.3 +/- 0.1 s). The magnitude of response in anaesthetised animals depended on anaesthetic depth. Mechanical stimulation of the cornea evoked a bradycardia (-49.2 +/- 4.8 bpm) and an increase in respiratory cycle length from 4 +/- 0.36 to 5.88 +/- 0.2 s which was only present in the WHBP. In the WHBP activation of forelimb and corneal nociceptors both elicited significant pressor effects; in anaesthetised rats there were inconsistent changes in arterial pressure. To determine a role for the nucleus of the solitary tract (NTS) in mediating nociceptive evoked responses in the WHBP, synaptic transmission was blocked reversibly following bilateral microinjections of cobalt chloride. The heart rate responses evoked from either forelimb or corneal nociceptors were attenuated by approximately 50% (P < 0.05). A similar effect was observed using isoguvacine, a GABAA receptor agonist, to hyperpolarise NTS neurones. In conclusion, activation of forelimb and corneal nociceptors evoked contrasting patterns of cardiorespiratory response in the WHBP while in the anaesthetised rat the magnitude of the cardiorespiratory response to forelimb stimulation was quantitatively dependent on anaesthetic dose. In the WHBP, NTS neurones appear important for mediating the cardiac component of the reflex response following stimulation of nociceptive reflex pathways.     

Respiratory sinus arrhythmia and the heart rate response to carotid baroreceptor activation after hard dynamic exercise in humans

The aim of this study was to examine the influence of 20 min of hard exercise (HR>160 beats min(-1)) on the efficacy of the cardiac parasympathetic nervous control of heart rate in humans (20-31 years; of either sex). This intensity of exercise was chosen to produce strong activation of the cardiac sympathetic nerves. Using well-controlled stimulus parameters, the efficacy of cardiac parasympathetic control of heart rate was assessed by recording the heart rate response to carotid baroreceptor activation (CBR) and the amplitude of respiratory sinus arrhythmia (RSA). Measurements were made while the subject performed light exercise (100-135 beats min (-1)) before (Control 1) and after very brief (Control 2) and prolonged (20 min; post) periods of hard exercise. There was no difference in the CBR in the three different measurement periods; 0.33 +/- 0.17, 0.38 +/- 0.18 and 0.39 +/- 0.18 beats min(-1) mm Hg(-1) (mean +/- S.D., N=6) for Control 1, Control 2 and post, respectively. At a heart rate of 120 beats min (-1), amplitude of the RSA was 6.1 +/- 2.4, 5.6 +/- 2.4 and 3.3 +/- 2.1 beats min(-1) for Control 1, Control 2 and post, respectively (P<0.001 post vs. Control 1 and Control 2, N=8). The decrease in RSA amplitude following hard exercise may be attributable to an exercise-induced reduction in airway resistance and work of breathing. Overall, these results do not support the hypothesis that sustained hard exercise that produces strong activation of cardiac sympathetic nerves reduces cardiac parasympathetic efficacy.     

Modulation of cardiovascular and electrocortical activity through serotonergic mechanisms in the nucleus tractus solitarius of the rat

The nucleus tractus solitarius (NTS) is an integral part of the baroreceptor reflex arc. Thus, stimulation of the NTS elicits changes in arterial pressure and heart rate as well as in numerous other physiologic parameters including electrocortical activity. Serotonin (5-HT), which has been implicated in cardiovascular and electrocortical control, is present in nerve terminals within the NTS. Therefore, this study was designed to determine whether 5-HT may effect that control within the NTS. Serotonin injected into the NTS of anesthetized rats produced marked changes in the EEG, arterial pressure, and heart rate. EEG activity changed from irregular 1-5 Hz, 350-500 microV waves with an overlying 13-15 Hz, low voltage rhythm to a regular, 5 Hz, 250-300 microV rhythm. The dose-dependent cardiovascular changes were maximal at a dose of 400 pmol which produced a fall of mean arterial pressure of 48 +/- 2 mm Hg from a baseline of 96 +/- 4 mm Hg and of heart rate of 90 +/- 9 bpm from a baseline of 400 +/- 18 bpm (n = 6; P less than 0.001). Both the cardiovascular and EEG effects of 5-HT injected into the NTS were blocked by the prior injection of the 5-HT antagonist metergoline at the same site. However, the bilateral microinjection of metergoline into the NTS did not affect the baroreceptor reflex. Thus, although serotonergic mechanisms in the NTS may be involved in the modulation of electrocortical and cardiovascular activity, they are not integral to the baroreceptor reflex arc.     

Antagonism of the baroreceptor reflex by glutamate diethyl ester, an antagonist to L-glutamate

Recent reports have suggested that the excitatory amino acid L-glutamate is a neurotransmitter released by baroreceptor afferent nerves at their termination in the nucleus tractus solitarii (NTS). In this study we have examined the effect on arterial pressure, heart rate and baroreflex activity of the glutamate antagonist glutamate diethyl ester (GDEE) microinjected into the NTS of 50 rats anesthetized with Chloralose. Bilateral injections of GDEE produced dose dependent transient hypertension. The threshold dose was 2.5 micrograms/NTS and at a dose of 15 micrograms/NTS a maximal rise in arterial pressure and heart rate (from 95 +/- 8.7 mm Hg to 153 +/- 6.4 mm Hg and from 322 +/- 14.7 beats/min to 364 +/- 16.2 beats/min respectively, P less than 0.001, n = 6) occurred. A dose of 15 micrograms/NTS also completely blocked the baroreflex when injections were made bilaterally and it totally antagonized the cardiovascular effects of L-glutamate when injected immediately prior to L-glutamate. The hypertension, the antagonism of L-glutamate, and the blockade of the baroreflex persisted for 20-30 min. In that L-glutamate mediates a baroreflex-like response upon injection into NTS and in that GDEE blocks that response while at the same time blocking the naturally occurring baroreflex, the data are consistent with L-glutamate being a neurotransmitter of baroreflex afferents.     

Somatosympathetic reflex in a working heart-brainstem preparation of the rat

The purpose of the present study was to examine the cardiorespiratory responses (CR) evoked by a somatosympathetic reflex (SSR) in the working heart-brainstem preparation (WHBP). Sprague-Dawley rats (75-100 g) were anesthetized with halothane, bisected sub-diaphramatically and decerebrated pre-collicularly (n = 15). The preparation was transferred to a recording chamber and perfused via the thoracic aorta with Ringer's solution containing an oncotic agent (Ficoll, 1.25%). SSR was activated by electrical stimulation (5 s) of the brachial nerve (0.5-40 Hz, 1-20 V, 0.1 ms) or the forelimb (0.5-40 Hz, 5-60 V, 2 ms). Stimulation at 40 Hz significantly increased heart rate (HR, 366 +/- 10 to 374 +/- 9 beats/min), systemic perfusion pressure (PP, 83 +/- 5 to 89 +/- 6 mmHg) and phrenic nerve discharge (PND, 0.4 +/- 0.1 to 1.4 +/- 0.3 Hz). Ganglionic blockade with hexamethonium (300 microM) eliminated the tachycardia and pressor response but did not alter the tachypnea to forelimb stimulation (n = 3). Transection of the brachial nerve plexus abolished the increase in PP and PND (n = 4). This indicates that a neural reflex mediated these responses. Spinal transection (C1-C2) completely abolished all responses indicating that they were mediated via a supraspinal pathway (n = 2). Based upon these findings, we conclude that activation of somatosensory afferent fibers in the WHBP evokes a programmed pattern of autonomic responses altering the activity-state of both the cardiovascular and respiratory systems. The WHBP provides a unique opportunity to investigate the medullary circuits and neuronal mechanisms that may be involved in coupling cardiorespiratory and somatomotor activity during locomotion/exercise.     

Effect of pentobarbital anesthesia on renal sympathetic nerve activity in the rabbit

The effects of pentobarbital (PB) anesthesia on arterial pressure, heart rate, and renal nerve activity (RNA) were studied in chronically instrumented intact rabbits and rabbits with sinoaortic baroreceptor denervation (SAD). In intact rabbits, PB caused an initial decrease in mean arterial pressure from 82 +/- 2 to 42 +/- 5 mm Hg, which then returned to the control level within 5 min. RNA increased by 144 +/- 19% in response to hypotension induced by PB then also returned to the control level within 5 min. Heart rate increased by 56 +/- 10 from 244 +/- 11 beats/min and remained elevated for 60 min. Sensitivities of baroreflex control of heart rate and RNA were markedly impaired by PB anesthesia. In SAD rabbits, PB caused hypotension (-46 +/- 5 mm Hg), which lasted for 15 min. RNA decreased initially by 80 +/- 5%, then gradually returned toward the control level. However, at 45 min after injection of PB, RNA was still depressed significantly. Tachycardia induced by PB was abolished by SAD, i.e. heart rate actually decreased by 53 +/- 10 beats/min. These results suggest that in intact rabbits steady-state effects of PB were: no change in mean arterial pressure or RNA, and tachycardia, all due to baroreflex compensation. However, in the absence of baroreflex compensation, PB elicited hypotension, bradycardia, and a decrease in RNA.     

Postnatal development of blood pressure and baroreflex in mice.

Postnatal development of blood pressure, heart rate and their regulation by arterial baroreceptor reflex in mice was examined. We first confirmed that simultaneous recordings of pulsatile blood pressure by the "servo null" method and the conventional catheter method gave almost identical tracings in halothane-anesthetized adult mice. We then measured blood pressure by servo null method together with electrocardiograph in mice of various ages from newborn to adult. Mean blood pressure increased progressively with age from 19 + 2 mm Hg in P0 newborn to 74+/-1 in adult mice, while heart rate initially increased from 365+/-12 bpm in newborn to 441+/-15 in infant (7 days old), and then decreased to 337+/-15 in adult mice. Between 1 and 2 weeks of age, gain of arterial baroreceptor reflex abruptly increased from a newborn value of 0.3 to a near adult value of 1.1 ms/mm Hg. On the other hand, sensitivity to anesthesia did not differ except for P1 and P2 newborns. We conclude that pulsatile blood pressure can be accurately measured by the servo null method even in the newborn mice and that baroreflex heart rate control mature at around 2 weeks after birth in the mice.     

Cardiorespiratory reflexes in mice

The various transgenic strains of mice make this species an attractive experimental model. We compared qualitatively some cardiorespiratory reflexes in two different preparations of mouse: in vivo urethane anaesthetised and a working heart-brainstem preparation (WHBP). Cardiorespiratory reflexes were evoked by stimulating baroreceptors, pulmonary vagal C fibres and cardiac receptors in both preparations, while peripheral chemoreceptors were also stimulated in the WHBP. In anaesthetised mice, activation of baroreceptors, pulmonary C fibres and cardiac receptors evoked an atropine-sensitive bradycardia (range: 21–414 bts/min) and depressed ventilation. A reflex fall in arterial pressure was also observed during pulmonary C fibre and cardiac receptor stimulation. Similar reflex bradycardia (range 81–164 bts/min) and respiratory responses were observed in the WHBP following stimulation of baro-, pulmonary C fibre and cardiac receptors. Additionally, sodium cyanide stimulation of peripheral chemoreceptors in the WHBP produced an atropine-sensitive bradycardia and increased respiratory frequency and amplitude. Thus, the cardiorespiratory reflex responses elicited in the mouse are similar to those reported in other species. It is concluded that the qualitatively similar reflex performances between the in vivo anaesthetised mouse and the WHBP make the latter an adequate model for studying central mechanisms controlling the cardiorespiratory system.     

The mechanism of the vagal bradycardia evoked by diencephalic stimulation in the rabbit

Blood pressure, in the rostral arterial system, was varied in the range 38-122 mm Hg by impeding the flow through the descending thoracic aorta in rabbits, anaesthetized with urethane and chloralose, in whom the spinal cord had been transected at mid-cervical level. Resting heart rate (H.R.) varied inversely with mean rostral arterial blood pressure (B.P.). The linear regression of H.R. on B.P. had a slope that averaged -0.38 beats X min-1 X mm Hg-1. Electrical stimulation in the lateral hypothalamic area, using 10 s trains of 300 microA X 1 ms constant current cathodal pulses at 60 Hz, caused H.R. to slow, provided that B.P. was above a threshold value and that the baroreceptor afferent pathway was intact. The mean threshold pressure was 49.5 mm Hg. Above threshold, the linear regression of the fall in H.R. during stimulation (delta H.R.) on B.P. had a slope that averaged -1.33 beats X min-1 X mm Hg-1. Linearity was good (r = 0.96). The results suggest that an inflow of baroreceptor impulses is essential for electrical stimulation of the cardioinhibitory region in the lateral hypothalamic area of the rabbit to cause bradycardia. This action is brought about by an increase in the gain of the vagal cardiodecelerator limb of the baroreceptor reflex.     

Baroreflex control of renal sympathetic nerve activity and spontaneous rhythms at Mayer wave's frequency in rats

The effects of sedation with pentobarbital sodium (15 mg/kg followed by 15.9+/-1.2 mg/kg/h, i.v.) on arterial pressure (AP) Mayer waves and accompanying oscillations of renal sympathetic nerve activity (RSNA) were examined in rats (n=8). As compared with values observed in the conscious state, pentobarbital significantly (P<0.05) decreased AP (from 119+/-2 to 93+/-3 mm Hg), heart rate (HR; from 427+/-11 to 355+/-11 beats/min) and RSNA (from 1.20+/-0.27 to 0.62+/-0.13 microV). The baroreflex control of RSNA was analyzed by fitting a sigmoid logistic function to changes in RSNA and AP observed during nitroprusside and phenylephrine administrations. During pentobarbital infusion, the RSNA-AP relationship was reset towards lower AP values, but neither its maximum gain nor its gain at resting AP were significantly altered (from 6.3+/-1.0 to 5.8+/-1.4 and from 3.2+/-0.5 to 3.8+/-1.3 normalized units (n.u.)/mm Hg, respectively). Spectral power in the frequency band containing Mayer waves (0.29-0.73 Hz) was significantly decreased by pentobarbital for both AP (from 4.65+/-0.90 to 0.95+/-0.25 mm Hg2) and RSNA (from 1437+/-245 to 488+/-79 n.u.2). This effect was mainly secondary to the attenuation of strongly coherent oscillations of both variables at approximately 0.4 Hz. Although previous experimental evidence points to a major involvement of the sympathetic limb of the arterial baroreceptor reflex in the genesis of Mayer waves, the present study indicates that the amplitude of these oscillations cannot be used as a quantitative index of sympathetic baroreflex sensitivity.     

Neurogenic cardiac arrhythmias in acute intracranial increase in pressure (recurrent hemorrhage in subarachnoid hemorrhages)

Neurogenic cardiac arrhythmias during 5 cases of subarachnoid rebleeding in 4 patients were analyzed by using long-term ECG (Holter). The initial onset of rebleeding was characterized by an abrupt decrease of heart rate from 93.3 +/- 7.85 (beats/min) to 63.3 +/- 14.6 (beats/min). This was immediately followed by pronounced tachycardia of 163.0 +/- 20.9 (beats/min) and subsequently, alterations of the P wave, ST depression with an increase in T wave amplitude. Frequent premature ventricular contractions, couplets, and self-terminating episodes of ventricular tachycardia for 2-8 minutes were observed during 2 episodes of rebleeding, an idioventricular rhythm in one case. The ECG returned to normal in the 3 non-lethal cases. Pathogenetically, the initial heart rate decrease with varying P wave configuration can be explained through activation of the baroreceptor reflex. Elevated intracranial pressure causes a blood pressure increase thus stimulating the baroreceptors and consequently, the afferent and efferent tracts of the vagus nerve. The sympathicotonus appears to have a modulating effect.     

Opposite to alpha2-adrenergic agonists, an imidazoline I1 selective compound does not influence reflex bradycardia in rabbits

This work aimed to study the respective effects of central alpha2-adrenergic receptors (alpha2-ARS) and I1 imidazoline receptors (I1Rs) in the facilitatory effects of imidazoline-like drugs on the reflex bradycardia (RB). Experiments were performed in anaesthetized rabbits. The reflex bradycardic response was induced by phenylephrine injected i.v. LNP 509, rilmenidine and dexmedetomidine were administered intracisternally (i.c.). LNP509 (1 mg/kg, i.c.), a ligand highly selective for I1Rs, induced hypotension (54+/-3 vs. 93+/-2 mm Hg) and bradycardia (260+/-13 vs. 322+/-13 beats/min) (p<0.05, n=5) but did not affect RB. Rilmenidine (1 microg/kg, i.c.), a hybrid ligand which binds to both I1 and alpha2-ARS, also decreased arterial pressure (61+/-2 vs. 101+/-2 mm Hg) and heart rate (260+/-4 vs. 308+/-8) (p<0.01, n=5); it potentiated the RB (maximum R-R interval: 284+/-17 vs. 196+/-6 ms) (p<0.05, n=5). Dexmedetomidine (1 microg/kg, i.c.), a ligand selective for alpha2-ARs, reduced blood pressure (53+/-3 vs. 104+/-2 mm Hg) and heart rate (246+/-4 vs. 312+/-8 beats/min) (p<0.05, n=5) and potentiated the RB (maximum R-R interval: 518+/-38 vs. 194+/-4 ms) (p<0.05, n=5). The potentiation of RB was much greater than that observed with rilmenidine and was significantly prevented by L-NNA injected centrally. This study shows that: (i) an exclusive action on I1Rs which decreases arterial pressure, does not potentiate the RB ii) activation of alpha2-ARs potentiates the RB (iii) the R-R prolongation caused by alpha2-ARs stimulation is prevented by central NOS inhibition.     

Pressor responses of angiotensin II microinjected into the dorsomedial medulla of the dog

Angiotensin II (Ang II) was injected into regions of the dorsomedial medulla of dogs where both specific Ang II binding and neural elements containing this peptide are found. Picomole amounts of the peptide were delivered simultaneously from a linear array of 3 micropipettes with tips positioned concurrently in either the area postrema (ap), nucleus tractus solitarii (nTS), dorsal motor nucleus of the vagus (dmnX), or hypoglossal nucleus (nXII). Significant increases in blood pressure occurred with Ang II injections into the medial nTS (+12 +/- 2 mm Hg), the ap(+9 +/- 3 mm Hg), and the nXII (+6 +/- 2 mm Hg). In both the medial nTS and the nXII, the pressor responses were accompanied by significant increases in heart rate (+13 +/- 3 beats/min and +8 +/- 3 beats/min, respectively). Ang II injected into the dmnX did not produce consistent effects on blood pressure or heart rate. These data demonstrate that unilateral injections of picomole amounts of Ang II produce changes in blood pressure and heart rate which involve neural elements in the ap and medial nTS.     

Chemical stimulation of the area postrema induces cardiorespiratory changes in the cat

The purpose of our study was to determine the cardiorespiratory effects of exciting cell bodies of the area postrema of the cat. This was accomplished by local application of L-glutamic acid (bilateral application of 5 microliter of a 250-1000 mM solution) and kainic acid (bilateral application of 5 microliter of a 40 mM solution) to the area postrema of chloralose-anesthetized cats while monitoring arterial pressure, heart rate, tidal volume and respiratory rate. These excitatory amino acids activate neuronal cell bodies but not axons of passage. L-Glutamic acid produced a dose-dependent increase in arterial pressure, decreases in respiratory rate and minute volume and, occasionally, ventricular tachyarrhythmias. Kainic acid produced effects similar to those seen with L-glutamic acid except the changes in respiratory activity were more pronounced with each animal exhibiting respiratory arrest. In artificially respired animals, kainic acid produced similar cardiovascular changes as those occurring in spontaneously breathing animals (i.e. increases in arterial pressure of 61 +/- 5.7 mm Hg, and in heart rate of 32 +/- 8.3 beats/min). Finally, application of kainic acid to the area postrema abolished the pressor and tachycardic responses to bilateral occlusion of the carotid arteries. These results suggest that activation of cell bodies in the area postrema can result in pronounced cardiorespiratory changes.     

Involvement of I(1)-imidazoline receptors in baroreceptor reflex in the caudal ventrolateral medulla of rats

There is ample evidence to show the existence of center I(1)-imidazoline receptors that are involved in the regulation of cardiovascular activities. The purpose of this study was to examine the possible role of I(1)-imidazoline receptors and alpha(2)-adrenoceptors within the caudal ventrolateral medulla (CVLM) in mediating the baroreceptor reflex in anesthetized rats. Unilateral microinjection of idazoxan (2 nmol in 50 nl), a mixed antagonist of I(1)-imidazoline receptors and alpha(2)-adrenoceptors, into the CVLM significantly (P<0.01) decreased blood pressure (BP), heart rate (HR), and the firing rate of presympathetic neurons in the rostral ventrolateral medulla (RVLM) by 21+/-6 mmHg, 25+/-5 beats per min and 3.5+/-0.9 spikes/s, respectively. Moreover, unilateral injection of idazoxan into the CVLM significantly (P<0.01) reduced the inhibitory responses of the ipsilateral RVLM presympathetic neurons evoked by stimulation of aortic nerve and elevation of BP, and partially inhibited the neuronal cardiac cycle-related rhythm. Depressor responses evoked by aortic nerve stimulation were significantly (P<0.01) attenuated 10 and 20 min after bilateral microinjection of idazoxan (2 nmol in 50 nl for each side) into the CVLM (-20+/-4 and -30+/-4 vs. -40+/-1 mmHg). However, injection of yohimbine (500 pmol in 50 nl), a selective alpha(2)-adrenoceptor antagonist, into the CVLM did not affect the resting cardiovascular activities and baroreceptor reflex. It is concluded that the CVLM I(1)-imidazoline receptors are involved in maintenance of tonic cardiovascular activities and transmission of the baroreceptor reflex.     

The reflex bradycardia evoked by brain ischemia and its relation to aortic A- and C-fiber baroreceptors.

In urethane-anesthetized rabbits with the right aortic nerve (RAN) sectioned, we examined the reflex heart rate (HR) responses during brain ischemia for approximately 30 s, by applying the anodal block to the unsectioned left aortic nerve (LAN) and, subsequently, by denervating the LAN. The maximum decreases in HR occurred at around 30 s after the onset of brain ischemia. The anodal block used in this study selectively inhibited the aortic A-fiber conduction but did not inhibit the volley of aortic C-fibers. The maximum HR fall responses to brain ischemia with and without the anodal block were 143 +/- 7 and 183 +/- 7 beats/min, respectively. When the maximum value of HR fall during brain ischemia in the absence of aortic nerve signals was subtracted from these two values, the reflex HR fall responses to brain ischemia with aortic C and A baroreceptor activation were 98 +/- 7 and 43 +/- 8 beats/min, respectively. In another series of experiments used for the same techniques, the reflex fall in HR seen during brain ischemia with the anodal block was totally abolished by vagotomy. The results indicate that the ability of aortic C baroreceptors becomes more prominent on the magnitude of brain ischemia-induced reflex bradycardia as compared to that of aortic A baroreceptors.     

Hypoventilation recruits preganglionic sympathetic fibers with inspiration-related activity in the superior cervical trunk of the rat.

Activity in preganglionic sympathetic neurons projecting in the cervical sympathetic trunk (CST) of rats was analysed with respect to changes in the pattern of the respiratory modulation during a long lasting hypoventilation. Under normal acid-base status (pH: 7.36+/-0.04, pCO2: 42.1+/-6.1 mm Hg, pO2: 135.8+/-43 mm Hg) a maximum of activity during expiration (expiration-related activity) was observed in all nerve recordings (n = 27). No other pattern of respiratory modulation was observed under this condition. Under a hypoventilation a dissociation between the duration of phrenic nerve activity and that of the inspiratory inhibition in neurons with expiration-related activity was observed as the inhibition was significantly prolonged by 49+/-24.9% and outlasted inspiration in 5/7 multifibers. When acid-base status was systematically changed (pH: 7.15+/-0.05, pCO2: 80.4+/-11.8 mm Hg, pO2: 62.8+/-17.5 mm Hg [n = 7]) by a hypoventilation lasting for several hours activity with a maximum peak during central inspiration (inspiration-related activity) emerged and disappeared when control conditions were reestablished. Neurons with expiration-related activity showed a cardiac rhythmicity (CR) of 62.5+/-14.6% (n = 27) and were inhibited to baroreceptor stimulation whereas neurons with inspiration-related activity showed no discernible CR (23.1+/-5.1%; n = 7) and were not inhibited to baroreceptor stimulation. Furthermore, expiration-related neurons were inhibited by 32.5+/-18.3% (n = 27) during noxious cutaneous stimulation while neurons with inspiration-related activity were activated by 21.5+/-12.1% (n = 7). These findings suggest that the respiratory modulation of preganglionic sympathetic activity in the CST consists of expiration-related activity in normal acid-base status. During hypoventilation neurons with inspiration-related activity are recruited. These neurons show reflex patterns distinct from expiration-related neurons and probably constitute a subgroup of sympathetic neurons which is activated under increased respiratory drive.     

The effect of coronary artery occlusion on the cardiovascular response to an aversive stress

The cardiovascular response to a controlled aversive stress was investigated both before and during acute myocardial ischemia. Classical aversive conditioning (a 30-s tone reinforced with a 1-s shock) served as the model of stress while anterior wall myocardial ischemia was induced by the occlusion (hydraulic occluder) of the left anterior descending coronary artery. The conditional response consisted of significant increases (P less than 0.01) in mean arterial pressure (AP, 13.8 +/- 1.9 mm Hg, 14.3%), left ventricular (LV) dP/dtmax (1300 +/- 324 mm Hg/s, 34.7%) and heart rate (HR, 44 +/- 4 beats/min, 46.8%). Mean coronary vascular resistance significantly (P less than 0.01) increased first (CVR, 0.52 +/- 0.18 mm Hg/ml/min, 17.2%), then decreased (0.77 +/- 0.14 mm Hg/ml/min, 25.5%). In contrast, during acute myocardial ischemia both the HR and d(LVP)/dtmax conditional response were significantly reduced (P less than 0.01) by 58 and 54%, respectively (HR, 20.7 +/- 3.8 beats/min, d(LVP)/dt, 756 +/- 226 mm Hg/s). In addition, the initial CVR increase was virtually eliminated (0.13 +/- 0.10 mm Hg/ml/min, 74.0% reduction) while the CVR decrease was significantly reduced (P less than 0.01) by 48% (0.40 +/- 0.15 mm Hg/ml/min) during the coronary occlusion. The mean AP response, however, was not affected by myocardial ischemia. The pre-conditional stimulus cardiovascular variables were similarly unaffected by the coronary artery occlusion. Thus, coronary artery occlusion attenuated both the coronary and cardiac response elicited by an aversive stress. The mechanism mediating this inhibition of the conditional response remains to be determined but may involve the activation of vagal depressor reflexes during the acute ischemia.     

Activation of gastric afferent fibers increases coronary arterial resistance in anesthetized dogs

Stimulation of chemically sensitive receptors in the stomach with capsaicin is known to reflexly increase heart rate, arterial pressure, left ventricular contractility, and systemic vascular resistance. What is not known, however, is if activating these gastric afferents can also evoke reflex changes in coronary arterial resistance. Therefore, in 24 chloralose-anesthetized dogs, we used a Gregg cannula and a constant flow preparation to assess left circumflex coronary arterial (LCCA) resistance while stimulating chemically sensitive gastric receptors with capsaicin. Capsaicin (60 micrograms), applied topically to the serosal surface of the stomach, produced significant (P less than 0.05) increases in heart rate (8 +/- 2 bpm), mean arterial pressure (22 +/- 1 mm Hg), LCCA pressure (7 +/- 1 mm Hg), and LCCA resistance (0.30 +/- 0.04 mm Hg/ml/min). These responses were still present after bilateral thoracic vagotomy, but were eliminated by bilateral thoracic splanchnicotomy. alpha-adrenergic blockade eliminated and beta-adrenergic blockade enhanced the increases in LCCA pressure and resistance that were evoked by capsaicin. Thus, stimulating chemically sensitive receptors in the stomach can reflexly increase coronary arterial resistance by alpha-adrenergic vasoconstriction. The possibility exists, therefore, that physiological or pathological events which activate gastric afferents can affect reflexly the coronary circulation.