Enhanced heart rate response to haemorrhage by ileus in the pig

Effects of ileus on cardiovascular and hormonal responses to haemorrhage were evaluated in 10 anaesthetized pigs. Ileus was induced and the bleeding sequence repeated on the following day. Before ileus, a resting heart rate (HR) of 105 (range 83–140) beats min^-1 remained unchanged until haemorrhage amounted to 15% of the blood volume. With a blood loss of 28% HR increased to a maximum of 162 (126–245) beats min^-1. In contrast, ileus increased HR upon initiation of haemorrhage from a similar resting value to a maximum of 200 (152–250) beats min“¹ (P < 0.0005). There were neither statistical differences in mean arterial pressure, cardiac output, central venous pressure, thoracic electrical impedance, pulmonary arterial mean pressure, pulmonary wedge pressure, pulmonary and systemic vascular resistances, nor in plasma concentrations of dopamine, adrenaline, vasopressin and aldosterone during haemorrhage before and after ileus. Plasma noradrenaline increased more with haemorrhage after than before ileus: from 2.8 (1.2–5.0) to 13 (2.3–59.0) vs. 3.0 (1.5.2) to 3.6 (2.7–17.5) nmol l”¹ (P < 0.005). Also, the pancreatic polypeptide response to haemorrhage was enlarged with ileus (29 (0–60) to 90 (45–145) vs. 23 (0–64) to 57 (27–106) pmol l“¹ (P < 0.005)). No significant differences could be detected in cardiovascular and hormonal responses to haemorrhage before and after a sham-operation in three pigs. Results demonstrate an immediate and enhanced HR response to haemorrhage in the pig with ileus, reflected in sympathetic activation as indicated by plasma noradrenaline.     

Cardiovascular and catecholamine responses to static exercise in partially curarized humans

Neural control of the circulation was evaluated during static exercise in 19 subjects by the determination of heart rate (HR), mean arterial pressure (MAP), cardiac output (CO) and plasma catecholamines. Influence from central command was evaluated during contractions with weakened muscles following partial curarization and reflex influence from metaboreceptors was assessed by post-exercise muscle ischaemia. Static handgrip increased HR and more so MAP and CO and MAP remained elevated during post-exercise muscle ischaemia. With partial curarization plasma catecholamines were also increased (P<0.05). Two-leg extension increased all variables and during post-exercise muscle ischaemia elevations of HR, MAP and CO were maintained (P<0.05). With partial curarization HR, MAP and plasma noradrenaline were even greater during the contraction. With the involvement of both legs during static exercise, reflex influence from the muscles elevated blood pressure by way of HR and CO and the importance of central command was detectable for HR and MAP as plasma catecholamines became elevated. However, the results indicate a separation between a central command influence on HR and CO related to an increase in plasma catecholamines during a handgrip, while the reflex influence on blood pressure was directed towards total peripheral resistance.     

Cardiovascular and ventilatory responses to electrically induced cycling with complete epidural anaesthesia in humans

Cardiovascular and ventilatory responses to electrically induced dynamic exercise were investigated in eight healthy young males with afferent neural influence from the legs blocked by epidural anaesthesia (25 ml 2% lidocaine) at L3-L4. This caused cutaneous sensory anaesthesia below T8-T9 and complete paralysis of the legs. Cycling was performed for 22.7 ± 2.7 min (mean, SE) (fatigue) and oxygen uptake (Vo₂) increased to 1.90 ± 0.13 1 min^-1. Compared with voluntary exercise at the same Vo₂, increases in heart rate (HR) (135 ± 7 vs. 130 ± 9 beats min^-1) and cardiac output (16.9 ± 1.1 vs. 17.3 ± 0.9 1 min^-1) were similar, and ventilation (54 ± 5 vs. 45 ± 4 1 min^-1) was higher (P < 0.05). In contrast, the rise in mean arterial blood pressure during voluntary exercise (93 ± 4 (rest) to 119 ± 4 mmHg (exercise)) was not manifest during electrically induced exercise with epidural anaesthesia [93 ± 3 (rest) to 95 ± 5 mmHg (exercise)]. As there is ample evidence for similar cardiovascular and ventilatory responses to electrically induced and voluntary exercise (Strange et al. 1993), the present results support the fact that the neural input from working muscle is crucial for the normal blood pressure response to exercise. Other haemodynamic and/or humoral mechanisms must operate in a decisive manner in the control of HR, CO and VE during dynamic exercise with large muscle groups.     

The role of the adrenal medulla in cardiovascular responses to hypertonic saline in haemorrhaged conscious rats

The aim of this study was to determine if the adrenal medulla plays a role in mediating haemodynamic effects of hypertonic saline (HTS) resuscitation during haemorrhagic hypotension in conscious rats. Wistar-Kyoto rats were either adrenomedullectomized (ADMX, n = 11) or sham-operated (SHAM, n = 10) and implanted with intravascular catheters. Pre-haemorrhage resting mean arterial pressure (MAP) was lower in the ADMX than in the SHAM group. Haemorrhage was performed by withdrawal of blood through the venous catheter, and a MAP of 50 mmHg was maintained for 1 h by further withdrawal when necessary. Both groups responded to haemorrhage with marked bradycardia. Plasma adrenaline (A) rose 10-fold in response to hypotension in the SHAM group, while remaining at pre-haemorrhage levels in the ADMX group, indicating successful adrenal demedullation. Infusion of 2.0 ml kg^-1 HTS (NaCl 8.0 mg ml^-1 i.v.) produced an immediate increase in MAP and heart rate (HR) in both groups, to pre-haemorrhage values or higher. Plasma noradrenaline (NA) increased in both groups after HTS, while the high levels of A in the SHAM group slowly returned toward baseline. Plasma glucose and rate of haemodilution was higher in the SHAM group during and after hypotension. The maintenance of MAP above 60 mmHg was less effective in the SHAM group during the first 2 h after HTS, but after 24 h, pre-haemorrhage MAP was established in both groups. In conclusion, the adrenal medulla does not play a major role in the response to HTS resuscitation.     

Splanchnic and renal vasoconstrictor and metabolic responses to neuropeptide Y in resting and exercising man

The local clearance of neuropeptide Y (NPY) and whether NPY influences splanchnic and renal metabolism in man have not been investigated previously. The influence of NPY on splanchnic and renal blood flows at physiologically elevated levels has also not been investigated. The effects of a 40-min constant NPY infusion (3 pmol kg^-1 min^-1) at rest and during 130 min of exercise (50% of Vo_2max) were studied in six healthy subjects and compared with resting and exercising subjects receiving no NPY. Blood samples were drawn from arterial, hepatic and renal vein catheters for the determination of blood flows (indicators: cardiogreen and paraaminohippuric acid [PAH]), NPY, catecholamines, glucose, lactate and glycerol. NPY infusion was accompanied by: (1) significant fractional extraction of NPY-like immunoreactivity (NPY-Li) by splanchnic tissues at rest (58±5%) and during exercise (53±6%), while no arterial–venous differences could be detected across the kidney; (2) a reduction in splanchnic and renal blood flows of up to 18 and 13% respectively (P < 0.01–0.001) at rest without any additional changes during exercise; and (3) metabolic changes as reflected in: (a) a more marked fall in arterial glucose during exercise compared to the reference group (P < 0.05); (b) a 35% lower splanchnic glucose release (P < 0.01) during exercise due to diminished glycogenolysis (P < 0.01); and (c) a lower arterial lactate level (18%P < 0.05) together with unchanged splanchnic lactate uptake during exercise, suggesting reduced lactate production by extrahepatic tissues. The disappearance of plasma NPY-Li after the infusions was biphasic with two similar half-lives at rest (4 and 39 min) and during exercise (3 and 43 min).     

Thoracic impedance and pulmonary atrial natriuretic peptide during head-up tilt induced hypovolaemic shock in humans

Head up and down tilts were used for manipulating the central blood volume in eight volunteers. During head-up tilt thoracic electrical impedance (TI) increased from 36.7 (33.9–52.1) ohm (mean and range) to 41.9 (36.9–59.2) ohm, heart rate from 60 (49–72) to 80 (65–90) beats min^-1 (P < 0.05) and decreased again to 57 (48–67) beats min^-1 accompanying a fall in mean arterial pressure from 86 (76–97) to 54 (41–79) mmHg and in cardiac output from 9.2 (5.9–12.1) to 6.9 (3.4–8.8) 1 min-¹ (n= 7, P < 0.07). Central venous pressure did not change significantly. Pulmonary arterial mean, 6 (3–12) mmHg, and wedge pressures, 4 (1–9) mmHg, decreased to 4 (1–11) and 1 (0–7) mmHg, respectively, and mixed, 78 (77–79%), and central venous oxygen saturations, 72 (71–73)%, fell to 62 (46–75) and 54 (44–58)%, respectively (P < 0.05). Atrial natriuretic peptide (ANP) was determined from blood of the superior vena cava and pulmonary and brachial arteries. Pulmonary artery ANP, 18.4 (7.5–30.7) pmol l^-1, was higher than in vena cava, 13.3 (5.2–20.9) pmol 1^_1 (P < 0.05). At the time of presyncope, pulmonary artery ANP decreased from 20.8 (37.4–10.1) to 13.7 (19.7-5.7) pmol l^-1, in vena cava from 13.8 (23.1–7.1) to 10.2 (17.9-6.7) pmol l^-‘ and in the brachial artery from 16.9 (34.1–5.2) to 11.3 (18.5-5.1) pmol l“¹ (P < 0.05). Head-down tilt did not affect the recorded variables significantly. Thoracic electrical impedance, pulmonary artery pressure and venous oxygen saturations were sensitive indices of the central blood volume as reflected in the release of atrial natriuretic peptide from the right side of the heart.     

Vasopressin release induced by hemorrhage in the goat

Effects of moderate hemorrhage were studied in normovolemic and hydrated conscious goats. Plasma arginine vasopressin (AVP) in jugular vein blood did not rise in response to bleeding of 8 and 12 ml/kg b.wt. After a blood loss of 16 ml/kg an abrupt and conspicuous rise in plasma AVP (to > 10 times basic level) was seen in 50% of the experiments, whereas no rise in AVP occurred in the remaining experiments. Bleeding at 20 and 24 ml/kg gave a more consistent AVP response. Hydration did apparently not reduce the AVP-responsiveness to bleeding. The plasma vasopressin concentration returned to pre-hemorrhage level about 3 h after bleeding, i.e. before the blood was re-transfused. A minor, and inconsistent rise in plasma renin activity occurred in response to bleeding. Central venous pressure fell during hemorrhage and stayed depressed until the blood was re-transfused. Since the depression was of the same order in all experiments, and was still present when plasma AVP had returned to pre-hemorrhage level, the fall in venous pressure was obviously not the main cause of the AVP-response. However, the pronounced rise in plasma vasopressin was correlated to a fall in the arterial pressure and to hyperventilation. No urge to drink developed during any of the hemorrhage experiments. It is concluded that the goat does not readily respond to hemorrhage with vasopressin liberation. When it happens, pressor amounts of the hormone are released, and a fall in arterial pressure and/or increased stimulation of respiratory chemoreceptors (hypoxia?) appear(s) to be the ultimate cause(s) of the release. This thirst-independent regulation of vasopressin secretion is obviously of no importance in day to day control of water balance, but may help to maintain the arterial blood pressure in emergency situations.     

Vasopressin antagonist in nucleus tractus solitarius/vagal area reduces pressor and tachycardia responses to paraventricular nucleus stimulation in rats

In urethane-anesthetized rats, injections of 50 pmol of arginine-vasopressin (AVP) or thyrotropin-releasing hormone (TRH) into a lateral cerebral ventricle (i.c.v.) elicit short-latency increases in blood pressure. i.c.v. injection of 50 pmol of the AVP antagonist, d(CH2)5Tyr(Me)AVP, but not of the vehicle (artificial cerebrospinal fluid; a CSF), abolished the pressor action of i.c.v. AVP. The AVP antagonist did not antagonize the TRH-induced pressor responses. In another group of rats, a monopolar stainless-steel electrode was positioned stereotaxically in the paraventricular nucleus (PVN) and pressor responses were elicited by electrical stimulation of the PVN. Micro-injection of 1 nmol of the AVP antagonist, but not of aCSF alone, into the nucleus tractus solitarius/vagal area (NTS/VA), reduced PVN-stimulated pressor responses to 26 +/- 6% of control and stimulation-induced tachycardia to 37.3 +/- 9.0% of control. These studies indicate that the pressor and heart-rate responses to PVN stimulation may be mediated, in part, via AVP receptors in the NTS/VA.     

Cardiovascular responses in Type A and Type B men to a series of stressors

Fifty-six healthy adult males were administered the Type A Structured Interview and assessed as exhibiting either Type A (N=42) or Type B (N=14) behavior pattern. They were monitored for systolic (SBP) and diastolic blood pressure (DBP) and heart rate (HR) responses during a series of six challenging tasks: Mental Arithmetic, Hypothesis Testing, Reaction Time, Video Game, Handgrip, and Cold Pressor. The results indicated that Type A subjects exhibited greater cardiovascular responses than did Type B subjects during some (Hypothesis Testing, Reaction Time, Video Game and Mental Arithmetic) but not all (Handgrip and Cold Pressor) of the tasks. These results are discussed in terms of previously reported findings on conditions that do and do not produce differences in Type A/B cardiovascular stress responses. This research was supported by USPHS Grant MH-31269. We would like to thank Drs. Steve Manuck, David Krantz, Ted Dembroski, Curt Sandman, David Hothersall, and Gifford Weary for their helpful comments on an earlier draft of this paper.     

Cardiovascular responses during one- and two-legged exercise in middle-aged men

Eight healthy and regularly physically active men, 44–69 years old, performed one- and two-legged dynamic knee extension exercise at increasing work intensities, including one leading to exhaustion. Leg blood flow increased linearly in relation to work rate, reaching a peak value of 5.1 ±0.4 1 min^-1. With a mean weight of quadriceps femoris of 2.2 ±0.1 kg, a peak perfusion of 2.3 ±0.11 kg^-1 min^-1 was attained. The maximal leg oxygen uptake was 0.72 ±0.071 min^-1 (0.33 ±0.03 1 kg^-1 min^-1). At submaximal work the elevation in limb oxygen uptake accounted for between 70 and 100% of the rise in pulmonary oxygen uptake. Comparing two- with one-legged knee extension the cardiac output was 1.5 1 min^-1 higher at each work level, reaching 13.7±0.7 and 12.3 ± 1.0, respectively at exhaustion, leaving 3.5 and 7.2 1 min^-1 of blood flow to the remaining body (cardiac output –leg blood flow). The mean arterial pressure was 119 ±5 mmHg at rest and increased to 155 mmHg for both test modes at the maximal work rate. The femoral arterial and venous plasma concentrations of lactate, ammonia and noradrenaline were significantly higher for two-legged as compared with one-legged exercise at the maximal load performed. However, the rate of release per leg, for both lactate and ammonia, did not differ between the two test conditions. It is concluded that physically active middle-aged men, with a well-retained muscle mass, can maintain a high skeletal muscle perfusion, similar to that of young males. However, the blood flow is achieved with a higher mean arterial pressure and an elevated sympathetic activity, as reflected by noradrenaline in plasma and spillover from the exercising limb.     

Vascular fluid shifts and endocrine responses to exercise in the heat

Summary This study examines the relationships between vascular changes and endocrine responses to prolonged exercise in the heat, associated with dehydration and rehydration by fluids of different osmolarity. Five subjects were exposed, in a 34 C environment for 4 h of intermittent exercise on a cycle ergometer at 85±12 Watts (SD). Fluid regulatory hormones and cortisol were analysed in 3 experimental sessions: one without any fluid supplement (NO FLUID), and two with progressive rehydration, either by spring water (WATER) or isotonic solution (ISO), given after 70 min of exercise. Results were expressed in terms of differences between the mean values observed at the end of the exercise and the first hour values taken as references.Dehydration (NO FLUID) elicited a 4.0±0.8% (SE) decrease in plasma volume (PV) and an increase in osmolarity (8.4±3.1 mosmol · l^–1). Concomitantly, plasma aldosterone (PA), renin activity (PRA), arginin vasopressin (AVP) and cortisol (PC) levels increased greatly in response to exercise in the heat (PA: 37.2+-10.8 ng. 100 ml^–1; PRA: 13.4±2.5 ng · ml^–1 · h^–1; AVP: 3.8±1.3 pg · ml^–1; PC: 12.2±2.7 g · 100 ml^–1). Rehydration with water led to decreased osmolarity (–8.2±2.1 mosmol · l^–1) with no significant changes in PV. With ISO, PV increased by 6.0±1.3% and the decrease in osmolarity was –5.8±1.8 mosmol · l^–1. With both modes of rehydration, the increases in PRA, AVP and cortisol were blunted; only ISO prevented the rise in PA.These data indicate that prolonged exercise in moderate heat is extremely effective in increasing cortisol and fluid-electrolyte regulatory hormones in dehydrated subjects. Progressive rehydration with water or isotonic solution, in the absence of osmotic and volemic stimuli, prevents the hormonal increases.     

Blockade of 5-HT2A receptors suppresses hyperthermic but not cardiovascular responses to psychosocial stress in rats

The aim of this study was to determine whether 5-HT2A receptors mediate cardiovascular and thermogenic responses to acute psychological stresses. For this purpose, adult male Wistar hooded rats instrumented for telemetric recordings of either electrocardiogram (ECG) (n=12) or arterial pressure (n=12) were subjected, on different days, to four 15-min episodes of social defeat. Prior to stress, animals received s.c. injection of the selective 5-HT2A receptor antagonist SR-46349B (trans-4-((3Z)3-[(2-dimethylaminoethyl)oxyimino]-3-(2-fluorophenyl)propen-1-yl)-phenol, hemifumarate) (at doses of 0.3, 1.0 and 3.0 mg/kg) or vehicle. The drug had no effect on basal heart rate or heart rate variability indexes, arterial pressure, and core body temperature. Social defeat elicited significant and substantial tachycardic (347±7 to 500±7 bpm), pressor (77±4 to 97±4 mm Hg) and hyperthermic (37.0±0.3 to 38.5±0.1 °C) responses. Blockade of 5-HT2A receptors, at all doses of the antagonist, completely prevented stress-induced hyperthermia. In contrast, stress-induced cardiovascular responses were not affected by the blockade (except small reduction of tachycardia by the highest dose of the drug). We conclude that in rats, 5-HT2A receptors mediate stress-induced hyperthermic responses, but are not involved in the genesis of stress-induced rises in heart rate or arterial pressure, and do not participate in cardiovascular control at rest.     

Cardiovascular responses to a quantified dose of nicotine as a function of personality and nicotine tolerance

Correlations between cardiovascular effects of a quantified dose of nicotine and personality measures previously shown to predict coronary heart disease were obtained. Thirty male smokers smoked a popular brand of a regular strength cigarette (1.0 mg FTC-estimated nicotine delivery) on one occasion and a nicotine-free cigarette on another occasion by means of a quantified smoke delivery system. Partial correlations controlling for effects of body weight, questionnaire-assessed nicotine tolerance, and cardiovascular responses to the nicotine-free control cigarette showed Jenkins Activity Survey Type A scores to correlate positively with nicotine-induced increase in diastolic blood pressure but negatively with nicotine-induced increase in systolic blood pressure. Partial correlations indicated that trait anxiety and depression were significantly associated with nicotine-induced heart rate increases but not with nicotine-induced blood pressure responses.This work was supported by a grant from the Office of Research and Development Administration of Southern Illinois University at Carbondale. This article is based on the first author's thesis, which was supervised by the second author.     

Cardiovascular responses and the sense of effort during attempts to contract paralysed muscles: role of the spinal cord

To determine whether spinal transection affects the cardiovascular response and the sense of effort which accompany attempts to contract paralysed muscles in normal subjects, paraplegic patients tried to contract paralysed leg muscles. During attempted contractions, paraplegic subjects reported a sense of effort but did not change heart rate or blood pressure. However, these subjects had a normal cardiovascular response to handgrip contractions. These data suggest that pathways descending to and arising from the spinal cord below the lesion are required to generate a cardiovascular response but are not necessary for the sense of effort.     

Cardiovascular and endocrine responses to feeding in the young calf.

A number of cardiovascular and endocrine responses which occur during and after feeding in the unweaned calf are described. 2. There was a substantial increase in both heart rate and mean aortic blood pressure during feeding in these animals. This occurred within the first few seconds and persisted throughout the period of ingestion. 3. The concentrations of glucose, insulin and gastrin in arterial plasma rose abruptly during, or immediately after, feeding and elevated values persisted for at least 2 hr. A transient increase in glucagon concentration was also observed. In contrast, feeding appeared to produce no immediate rise in enteroglucagon concentration. 4. The adrenal output of glucocorticoids rose transiently in response to feeding but that of catecholamines was unaffected. 5. Cardiovascular responses to feeding were also examined in other species. In unweaned kids the changes were essentially similar to those observed in the calf but were less pronounced. In lambs a persistent hypertension occurred which was associated with a brief initial tachycardia. In adult dogs ingestion of solid food also caused tachycardia but although the aortic blood pressure rose for a short period at the beginning of feeding, hypotension developed thereafter. 6. The possibility that both the cardiovascular and endocrine responses, which occur during or immediately after feeding, are mediated by the autonomic nervous system is discussed.     

Cardiovascular responses after brisk finger movement and their dependency on the “eigenfrequency” of the baroreflex loop

The baroreflex is mainly involved in short-term blood pressure regulation and strongly influenced by activations of medullary circulation centres in the brain stem and higher brain centres. One important feature of the baroreflex is its strong preference for oscillations around 0.1 Hz, which can be seen as resonance or “eigenfrequency” (EF) of the control loop (so-called Mayer waves). In the present study we investigated beat-to-beat heart rate intervals (RRI) and arterial blood pressure (BP) changes after brisk finger movement and their relationship to the “eigenfrequency” determined by cross spectral analysis between RRI and arterial blood pressure time series of 17 healthy subjects. The analyses revealed significant correlations between BP response magnitude (r = 0.63, p < 0.01) respectively RRI response magnitude (r = 0.59, p < 0.05) and EF. This can be interpreted in such a way that subjects with a “high” EF (>0.10 Hz) elicit larger BP responses as well as larger RRI responses when compared to subjects with a “low” EF (<0.10 Hz).     

Cardiovascular and metabolic responses to noradrenaline in men acclimatized to cold baths

Summary The purpose of this study was to see whether artificial acclimatization to cold would reduce the pressor response to noradrenaline (NA) as natural acclimatization has been shown to do, and whether it would induce nonshivering thermogenesis. Three white men were infused with NA at four dosage levels between 0.038 and 0.300 g·kg^–1·min^–1 (2–23 g·min^–1), before and after artificial acclimatization to cold and again 4 months later when acclimatization had decayed. Acclimatization was induced by ten daily cold (15°Q baths of 30–60 min followed by rapid rewarming in hot (38–42°C) water, and was confirmed by tests of the subjects responses to whole-body cooling in air. Three control subjects also underwent the first and third tests. Acclimatization substantially reduced the pressor response to NA at 0.150 and 0.300 g·kg^–1·min^–1, confirming earlier findings by the same technique in naturally acclimatized men, and its decay increased this response to beyond its initial levels (P<0.05 for both changes). Acclimatization did not change the response to NA of heart rate, subjective impressions, skin temperature of finger and toe, pulmonary ventilation, or plasma free fatty acids and ketone bodies. At no time did NA increase oxygen consumption, or increase skin temperature or heat flow over reported sites of brown fat. These findings would seem to show that acclimatization to cold reduces sensitivity to the pressor effect of NA but does not induce nonshivering thermogenesis, and that the reduced sensitivity is replaced by a hypersensitivity to NA when acclimatization decays.     

Cardiovascular and behavioural responses to conditioned fear and restraint are not affected by retrograde lesions of A5 and C1 bulbospinal neurons

The aim of this study was to test a possible role of A5 neurons in the expression of the pressor and tachycardic responses to conditioned fear and restraint, two forms of psychological stress. Previous Fos studies have shown that the C1 adrenergic neurons and spinally projecting neurons in the vasopressor region of the rostral ventrolateral medulla are not activated by these two stressors, suggesting that these cardiovascular changes may be mediated by other premotor sympathetic (presympathetic) cell groups. The same studies also revealed that the A5 noradrenergic group was one of the main presympathetic cell groups to be activated in response to these two stressors. Thus, we hypothesized that the A5 group could mediate these cardiovascular responses. Conditioned fear and restraint were tested in rats implanted with radiotelemetric probes before and after retrograde lesion with the selective toxin anti-dopamine-β-hydroxylase-saporin bilaterally injected in the spinal cord at T2–T3. Six animals were selected that had the most extensive loss of spinally projecting catecholaminergic neurons: A5 (81%–95%) and rostral C1 (59%–86%, which would include most C1 bulbospinal neurons). However, despite this major loss of noradrenergic and adrenergic presympathetic neurons, the magnitude of the cardiovascular response to conditioned fear and restraint was the same before and after the lesion. Associated behavioural changes were not affected either. The results indicate that A5 presympathetic neurons are not essential for the expression of the tachycardic and pressor responses to conditioned fear and restraint. They also confirm that C1 bulbospinal neurons are not involved in these responses. The presympathetic neurons driving the tachycardic and pressor responses to conditioned fear and restraint must be elsewhere.