Long-lasting inhibition of the cardiovascular responses to glutamate and the baroreceptor reflex elicited by neuropeptide Y injected into the nucleus tractus solitarius of the rat.

Neuropeptide Y (NPY) microinjected unilaterally into the nucleus tractus solitarii (NTS) of anesthetized paralyzed rats elicits a gradual dose-dependent and reversible fall in arterial pressure (AP) and heart rate (HR) lasting 20 min. It also abolished the brief (less than 1 min) dose-dependent and reversible fall of AP and HR elicited by L-glutamate (L-Glu) injected into the nucleus. The blockade of L-Glu by NPY appeared gradually and was prolonged, lasting over 2 h, and recovering by 24 h. It was not replicated by desamido-NPY or galanin. Unlike 2% lidocaine it did not block the hypotension elicited by focal electrical stimulation at the injection site indicating the response was not that of a local anesthetic. Bilateral injection of NPY into the NTS resulted, after an initial fall, in an elevation of AP (+48 +/- 10.6 mmHg). At this time the reflex bradycardia evoked by elevating AP with phenylephrine was markedly reduced. We conclude that in the NTS, NPY antagonizes the actions of L-Glu and may attenuate baroreceptor reflexes. Since the NTS is richly innervated by NPY neurons and contains many NPY binding sites and since primary baroreceptor afferents appear to be glutamatergic the results suggested that NPY may serve in NTS as a long-term regulator of baroreceptor reflex activity.     

Synaptic plasticity in the amygdala in a visceral pain model in rats

The amygdala plays a key role in the emotional-affective component of pain. This study is the first to analyze synaptic plasticity in the central nucleus of the amygdala (CeA) in a model of visceral pain. Whole-cell patch-clamp recordings were made from neurons in the latero-capsular part of the CeA in brain slices from control rats and rats with zymosan-induced colitis (>6 h postinduction). Monosynaptic responses were evoked by electrical stimulation of afferents from the pontine parabrachial area (PB) and from the basolateral amygdala (BLA). Enhanced synaptic transmission was observed at the nociceptive PB-CeA synapse, but not at the polymodal BLA-CeA synapse, in rats with colitis. The frequency of action potentials evoked by direct current injection was increased in CeA neurons from colitis rats, suggesting enhanced neuronal excitability. Our results provide novel evidence for an important role of the CeA in visceral pain.     

Human investigations into the exercise pressor reflex

During exercise, neural input from skeletal muscles reflexly maintains or elevates blood pressure (BP) despite a maybe fivefold increase in vascular conductance. This exercise pressor reflex is illustrated by similar heart rate (HR) and BP responses to electrically induced and voluntary exercise. The importance of the exercise pressor reflex for tight cardiovascular regulation during dynamic exercise is supported by studies using pharmacological blockade of lower limb muscle afferent nerves. These experiments show attenuation of the increase in BP and cardiac output when exercise is performed with attenuated neural feedback. Additionally, there is no BP response to electrically induced exercise with paralysing epidural anaesthesia or when similar exercise is evoked in paraplegic patients. Furthermore, BP decreases when electrically induced exercise is carried out in tetraplegic patients. The lack of an increase in BP during exercise with paralysed legs manifests, although electrical stimulation of muscles enhances lactate release and reduces muscle glycogen. Thus, the exercise pressor reflex enhances sympathetic activity and maintains perfusion pressure by restraining abdominal blood flow, while brain, skin and muscle blood flow may also become affected because the reflex 'resets' arterial baroreceptor modulation of vascular conductance, making BP the primarily regulated cardiovascular variable during exercise.     

Arterial baroreceptor reflex control of heart rate in two species of turtle

Attempts were made to stimulate an arterial baroreceptor reflex in anesthetized and conscious pond turtles. In turtles anesthetized with either alpha-chloralose or pentobarbital, occlusion of the ascending or descending aortas produced no reflex heart rate (HR) changes. In pentobarbital-anesthetized turtles, direct electrical or mechanical stimulation of potential baroreceptor sites along the central aortic arches and carotid arteries produced no significant changes in either HR or blood pressure (BP). Occlusion of the common carotid arteries also produced no HR or BP changes. Intravenously administered nitroglycerin lowered BP but caused no reflex tachycardia in anesthetized turtles. Phenylephrine and angiotensin elevated BP in the anesthetized turtle but caused no reflex bradycardia. In conscious turtles phenylephrine increased BP and nitroglycerin decreased BP. Neither response produced a statistically significant HR change, although HR tended to decrease transiently with phenylephrine and increase with nitroglycerin. These HR changes were abolished by atropine. Rapid intra-arterial infusion of 6% dextran transiently raised BP but caused no reflex bradycardia. These experiments suggest that cardiovascular regulation in the turtle is accomplished without a major contribution from arterial baroreceptor reflexes.     

Modulatory effects of endothelin-1 on central cardiovascular control in rats

In urethane-anesthetized and immobilized rats, modulatory effects of endothelin-1 (ET-1) on central cardiovascular control were examined. An injection of 0.1 pmol of ET-1 into the cisterna magna caused immediate increases in arterial pressure (AP), renal sympathetic nerve activity (RSNA), and heart rate (HR) that lasted for 5-45 min. At doses of 1 and 10 pmol, intracisternal ET-1 elicited initial increases (phase I) followed by decreases in these variables below the pre-injection level (phase II). At the dose of 1 or 10 pmol, the arterial baroreceptor reflex was suppressed during the latter part of phase I and during phase II. The three variables subsequently returned to, or often exceeded, pre-injection levels in 30 to 60 min and reflex activity recovered (phase III). However, AP often remained below control throughout the 2-h observation period. Essentially identical responses to intracisternal ET-1 were observed in unanesthetized precollicular decerebrated or urethane-anesthetized rats. Application of a piece of filter paper soaked with 1 pmol of ET-1 to the ventral surface of the medulla (VSM) caused the pattern of changes similar to the following intracisternal injection. A microinjection of 4 pmol of ET-1 into the nucleus tractus solitarius (NTS) caused a moderate increase in RSNA with a minute fall in AP. Intrathecal administration of ET-1 resulted in moderate changes in AP and RSNA at the dose as high as 100 pmol. We conclude that intracisternally administered ET-1 modulates tonic and reflex control of AP and sympathetic vasomotor activity and that the VSM appears to be involved critically in this modulation.     

The reflex bradycardia during brain ischemia in the rabbit.

We examined the responses of whole aortic nerve activity, aortic baroreceptor activity, heart rate (HR), and arterial pressure (AP) to brain ischemia sustained for approximately 30 s in anesthetized spontaneously breathing rabbits. The minimum values of HR observed during brain ischemia were 76 +/- 11 beats/min (mean +/- S.E., n = 14) before sectioning the bilateral aortic nerve (BAN), and 161 +/- 12 beats/min after sectioning the left aortic nerve (LAN), and 225 +/- 11 beats/min after sectioning the LAN and right aortic nerve (RAN). Averages for reflex fall in HR during BAN, LAN, and RAN activation were 140 +/- 9, 78 +/- 7, and 62 +/- 7 beats/min, respectively, by subtracting the HR fall responses to brain ischemia in the absence of aortic baroreceptor afferents from their control values. The heights of the integrated whole left and right aortic nerve activities in systole slightly increased during brain ischemia, whereas the brain ischemia remarkably increased those activities during the diastolic phases. The brain ischemia induced a hysteresis in the mean AP-aortic barorecept or activity relationship. These results suggest that the total activity of aortic nerve fibers would determine the bradycardia evoked by brain ischemia and that the difference between the relative contributions of LAN and RAN on the brain ischemia-induced reflex bradycardia would reflect the total impulse frequency of aortic myelinated and non-myelinated fibers.     

Inhibition of arterial baroreceptor reflex during coronary artery occlusion.

The sensitivity of baroreceptor reflex during myocardial ischemia induced by acute occlusion of left anterior descending coronary artery (LAD) was studied in anesthetized, artificially ventilated, and thoracotomized dogs. Occlusion of LAD attenuated the baroreflex mediated changes in heart rate (HR) in response to changes in arterial pressure (AP) in the animals with intact autonomic nervous system (ANS). The HR increased significantly with the time of occlusion of LAD in control (ANS) as well as in beta-blocked group, suggesting vagal inhibition. In atropinized and vagotomized animals, the HR remained unchanged following LAD occlusion. In control group, the sensitivity of baroreflex mediated tachycardia response to hypotension and bradycardia response to hypertension, after 4 h of LAD occlusion, was reduced. In beta-blocked animals, the tachycardia response after LAD occlusion was drastically reduced to almost zero. The peak sensitivity of baroreflex bradycardia response was reduced in atropinized and vagotomized animals while the peak sensitivity of baroreflex tachycardia response increased after vagotomy. In contrast, bradycardia response was increased after beta-blockade. These data indicate that acute LAD occlusion attenuates arterial baroreflex control of HR and reduction of baroreflex sensitivity is mediated by parasympathetic efferents.     

Modulatory effects of rat endothelin on central cardiovascular control in rats

To characterize the modulatory action of rat endothelin (endothelin-3 or ET-3) on the cardiovascular control by the central nervous system (CNS), ET-3 was injected into the cisterna magna of urethane-anesthetized and immobilized rats. An injection of 100 pmol of ET-3 caused immediate rises in arterial pressure (AP), renal nerve activity (RNA), and heart rate (HR). These variables subsequently decreased and, in 5-20 min, fell below the pre-injection level. Simultaneously, the arterial baroreceptor reflex was almost totally suppressed. Although RNA and HR subsequently returned to, or often exceeded, pre-injection levels in 20 to 60 min and reflex activity recovered, AP sometimes remained below control for at least 2 h. A similar pattern of changes was elicited in unanesthetized precollicular decerebrated rats. The responses to ET-3 were abolished by hexamethonium chloride, but were not conspicuously altered by arginine vasopressin antagonist or angiotensin II antagonist. The CNS sites responsible for ET-induced changes were subsequently searched. Topical application of ET-3 to the ventral surface of the medulla (VSM) caused the pattern of changes in AP, RNA, and HR similar to that following intracisternal injection. Microinjection of ET-3 into the nucl. tractus solitarius (NTS) increased AP and RNA, whereas intrathecal administration of it decreased them. We conclude that intracisternally administered ET-3 centrally modulates both tonic and reflex control of AP by the sympathetic nervous system and that the VSM appears to be primarily responsible for the modulation, although NTS and spinal cord may also be involved in it.     

Somatosensory regulation of serotonin release in the central nucleus of the amygdala is mediated via corticotropin releasing factor and gamma-aminobutyric acid in the dorsal raphe nucleus

Noxious cutaneous stimulation increases, whereas innocuous cutaneous stimulation decreases serotonin (5-HT) release in the central nucleus of the amygdala (CeA) in anesthetized rats. In the present study, we investigated the contribution of corticotropin releasing factor (CRF) receptors and gamma-aminobutyric acid (GABA) receptors in the dorsal raphe nucleus (DRN) to those responses. Release of 5-HT in the CeA was monitored by microdialysis before and after 10-min stimulation by pinching or stroking. Increased 5-HT release in the CeA in response to pinching was abolished by CRF₂ receptor antagonism in the DRN. Decreased 5-HT release in the CeA in response to stroking was abolished by either CRF₁ receptor antagonism or GABA_A receptor antagonism in the DRN. These results suggest that opposite responses of 5-HT release in the CeA to noxious versus innocuous stimulation of the skin are due to separate contributions of CRF₂, CRF₁ and GABA_A receptors in the DRN.     

Chronic inhibition of standing behaviour alters baroreceptor reflex function in rats

Aim: To investigate whether daily orthostatic stress during development is an important factor affecting arterial baroreceptor reflex function, we examined the effect of chronic inhibition of upright standing behaviour on the baroreceptor reflex function in rats. Methods: Upright standing behaviour was chronically inhibited during the developmental period between 3 and 8 weeks of age in Sprague–Dawley rats and heart rate (HR) and aortic nerve activity in response to increased and decreased mean arterial pressure (MAP) was measured after the treatment period. Results: The baroreceptor cardiac gain in the rats grown without standing behaviour was significantly lower than the control rats grown in a normal commercial cage (1.0 ± 0.1 beats min^?1 mmHg^?1 vs. 1.6 ± 0.2 beatsmin^?1 mmHg^?1, P < 0.05). The range of HR change in the MAP–HR functional curve was also lowered by chronic inhibition of orthostatic behaviour (56.2 ± 5.9 beats min^?1) compared with that of the control rats (76.8 ± 6.9 beats min^?1, P < 0.05). However the aortic afferent function remained normal after the treatment period, indicating that the attenuated baroreceptor reflex function may be due to other mechanisms involving functional alterations in the cardiovascular centres, efferents and/or peripheral organs. Body weight and adrenal weight were not affected by the inhibition of orthostatic behaviour, suggesting that the animals were not exposed to specific stress by this treatment. Conclusion: These results indicate that active haemodynamic changes induced by orthostatic behaviour are an important factor for setting the basal level of reflex function during development. Moreover, our experimental model may be useful for studying mechanisms of attenuated baroreceptor reflex observed after exposure to a chronic inactive condition.     

Localization and action of adenosine A2a receptors in regions of the brainstem important in cardiovascular control

In vitro autoradiography and central microinjections of a P₁ adenosine A_2a receptor antagonist have been employed to investigate a possible role for centrally located adenosine A_2a receptors in modulation of the baroreceptor reflex. In vitro autoradiography using [¹²⁵I]4-(2-[7-amino-2-[2-furyl][1,2,4]triazolol[2,3-a][1,3,5]triazin-5-yl-amino]ethyl)phenol ([¹²⁵I]ZM241385), the high-affinity adenosine A_2a receptor antagonist, revealed a heterogeneous distribution of adenosine A_2a binding sites within the lower brainstem of the rat. Image analysis showed high levels of binding in rostral regions of both the nucleus tractus solitarius and the ventrolateral medulla. Intermediate levels of binding were observed in the commissural nucleus tractus solitarius and the dorsal vagal motor nucleus, with low levels of binding in caudal regions of the nucleus tractus solitarius and the ventrolateral medulla, and the hypoglossal nucleus. Unilateral microinjections of unlabelled ZM241385 into the nucleus tractus solitarius had no effect on baseline levels of arterial pressure, heart rate and phrenic nerve activity recorded in anaesthetized, artificially ventilated rats. However, microinjections of ZM241385 reduced the bradycardia evoked by stimulation of the ipsilateral aortic nerve. In contrast, ZM241385 had no effect on the depressor response or the reduction in phrenic nerve activity evoked by aortic nerve stimulation.Our results indicate that adenosine A_2a binding sites are located in a number of brainstem regions involved in autonomic function, consistent with the idea that adenosine acts as a neuromodulator of a variety of cardiorespiratory reflexes. Specifically, the data support the hypothesis that adenosine A_2a receptors located within the nucleus tractus solitarius are activated during baroreceptor stimulation and have an important modulatory role in the pattern of cardiovascular changes associated with this reflex.     

Involvement of oxytocin and its receptor in nociceptive modulation in the central nucleus of amygdala of rats

Studies have demonstrated that oxytocin plays important roles in pain modulation in the central nervous system. Oxytocin-ergic neurons are found in paraventricular nucleus and supraoptic nucleus of the hypothalamus. The oxytocin-ergic neurons send fibers from hypothalamus to amygdala and high density of oxytocin receptors are found in the central nucleus of amygdala (CeA). The present study was performed to investigate the influences of oxytocin and its receptors on nociceptive responses in the CeA of rats. Intra-CeA injection of 0.1, 0.5 or 1 nmol of oxytocin induced dose-dependent increases in the handpaw withdrawal latency induced by noxious thermal and mechanical stimulation in rats. The oxytocin-induced anti-nociception could be blocked by the selective oxytocin antagonist 1-deamino-2-d-Tyr-(Oet)-4-Thr-8-Orn-oxytocin. The present study demonstrated that oxytocin and its receptors are involved in nociceptive modulation in the CeA of rats.     

Somatostatin immunoreactivity in axon terminals in rat nucleus tractus solitarii arising from central nucleus of amygdala: coexistence with GABA and postsynaptic expression of sst2A receptor

Axon terminals synapsing on neurones in the nucleus tractus solitarii (NTS) that originate from the central nucleus of the amygdala (CeA) have been shown to contain gamma-aminobutyric acid (GABA) immunoreactivity. Here we investigated whether such terminals also contain somatostatin (SOM), a neuropeptide found in axons distributed throughout the NTS and in somata in the CeA, and known to modulate cardiovascular reflexes when microinjected into the NTS. With fluorescence microscopy, SOM immunoreactivity was seen in the varicosities of some axons throughout the NTS that were anterogradely labelled with biotin dextran amine injected into the CeA. Such varicosities were frequently observed in close proximity to dendrites of NTS neurones that were immunoreactive for the SOM receptor sst(2A) subtype, and in many cases also for catecholamine synthesising enzymes. In the caudal, cardioregulatory zone of NTS, SOM immunoreactivity was localised by electron microscopic pre-embedding gold labelling to boutons containing dense-cored and clear pleomorphic vesicles and forming symmetrical synapses, mostly onto dendrites. Additional post-embedding gold labelling for GABA suggested that a subpopulation (29%) of GABAergic terminals sampled in this area of NTS contained SOM. Almost all boutons anterogradely labelled from the amygdala were GABA-immunoreactive (-IR) and 21% of these were SOM-IR. A similar proportion of these boutons (22%) formed synapses onto dendrites containing immunoreactivity for the SOM receptor sst(2A) subtype. These observations provide evidence that some of the GABAergic projection neurones in the CeA that inhibit baroreceptor reflex responses in the NTS in response to fear or emotional stimuli could release SOM, which might modulate the activity of NTS neurones via an action on sst(2A) receptors.     

Effect of baroreceptor denervation on the autonomic control of arterial pressure in conscious mice

This study evaluated the role of arterial baroreceptors in arterial pressure (AP) and pulse interval (PI) regulation in conscious C57BL mice. Male animals, implanted with catheters in a femoral artery and a jugular vein, were submitted to sino-aortic (SAD), aortic (Ao-X) or carotid sinus denervation (Ca-X), 5 days prior to the experiments. After basal recording of AP, the lack of reflex bradycardia elicited by administration of phenylephrine was used to confirm the efficacy of SAD, and cardiac autonomic blockade with methylatropine and propranolol was performed. The AP and PI variability were calculated in the time and frequency domains (spectral analysis/fast Fourier transform) with the spectra quantified in low- (LF; 0.25-1 Hz) and high-frequency bands (HF; 1-5 Hz). Basal AP and AP variability were higher after SAD, Ao-X or Ca-X than in intact mice. Pulse interval was similar among the groups, whereas PI variability was lower after SAD. Atropine elicited a slight tachycardia in control mice but did not change PI after total or partial denervation. The bradycardia caused by propranolol was higher after SAD, Ao-X or Ca-X compared with intact mice. The increase in the variability of AP was accompanied by a marked increase in the LF and HF power of the AP spectra after baroreceptor denervation. The LF and HF power of the PI were reduced by SAD and by Ao-X or Ca-X. Therefore, both sino-aortic and partial baroreceptor denervation in mice elicits hypertension and a remarkable increase in AP variability and cardiac sympathetic tonus. Spectral analysis showed an important contribution of the baroreflex in the power of LF oscillations of the PI spectra. Both sets of baroreceptors seem to be equally important in the autonomic regulation of the cardiovascular system in mice.     

Evidence of N-methyl-D-aspartate receptor-mediated modulation of the aortic baroreceptor reflex in the rat nucleus tractus solitarii

Microinjections of N-methyl-D-aspartate (NMDA) into the medial area of the nucleus tractus solitarii (NTS) of the rat led to a decrease in arterial pressure and heart rate. The NMDA receptor antagonist 2-amino-5-phosphonovalerate (AP5) reduced the cardiovascular responses to NMDA. Depressor and bradycardic responses to aortic nerve stimulation were reduced by AP5 but not by a substance P antagonist, injected into the NTS. High K+ stimulation caused a calcium-dependent release of glutamate and aspartate from tissues in the area of the NTS. These results provide evidence of NMDA receptor-mediated modulation of the aortic baroreceptor reflex in the rat NTS.     

Effect of carotid sinus nerve stimulation pattern on cardiorespiratory responses.

The reflex responses to steady and intermittent stimulation of the carotid sinus nerve (CSN) were compared in anesthetized dogs. Intermittent stimulation was less effective than steady stimulation in reducing the arterial blood pressure, and the disparity was exaggerated after acute sinoaortic denervation. With the sinoaortic nerves intact, at low mean stimulation frequencies the heart rate responses were greater during intermittent than during steady CSN stimulation. At higher mean stimulation frequencies, however, steady CSN stimuli were more effective than were the intermittent type. After sinoaortic denervation, steady stimuli evoked greater heart rate responses than did intermittent stimuli over the entire mean frequency range studied. Reflex changes in respiratory depth and frequency were also greater during steady than during intermittent CSN stimulation. The greater efficacy of steady than of intermittent stimulation in evoking.the observed reflex cardiovascular and respiratory changes is probably ascribable to the pronounced frequency limitation at the first synapse of the baroreceptor reflex in the brain.     

Protein kinase A-dependent enhanced NMDA receptor function in pain-related synaptic plasticity in rat amygdala neurones

Mechanisms of pain-related plasticity in the amygdala, a key player in emotionality, were studied at the cellular and molecular levels in a model of arthritic pain. The influence of the arthritis pain state induced in vivo on synaptic transmission and N -methyl- d -aspartate (NMDA) receptor function was examined in vitro using whole-cell voltage-clamp recordings of neurones in the latero-capsular part of the central nucleus of the amygdala (CeA), which is now defined as the 'nociceptive amygdala'. Synaptic transmission was evoked by electrical stimulation of afferents from the pontine parabrachial area (part of the spino-parabrachio-amygdaloid pain pathway) in brain slices from control rats and from arthritic rats. This study shows that pain-related synaptic plasticity is accompanied by protein kinase A (PKA)-mediated enhanced NMDA-receptor function and increased phosphorylation of NMDA-receptor 1 (NR1) subunits. Synaptic plasticity in the arthritis pain model, but not normal synaptic transmission in control neurones, was inhibited by a selective NMDA receptor antagonist. Accordingly, an NMDA receptor-mediated synaptic component was recorded in neurones from arthritic animals, but not in control neurones, and was blocked by inhibition of PKA but not protein kinase C (PKC). Exogenous NMDA evoked a larger inward current in neurones from arthritic animals than in control neurones, indicating a postsynaptic effect. Paired-pulse facilitation, a measure of presynaptic mechanisms, was not affected by an NMDA-receptor antagonist. Increased levels of phosphorylated NR1 protein, but not of total NR1, were measured in the CeA of arthritic rats compared to controls. Our results suggest that pain-related synaptic plasticity in the amygdala involves a critical switch of postsynaptic NMDA receptor function through PKA-dependent NR1 phosphorylation.     

The area postrema and control of arterial blood pressure; Absence of hypertension after excision of the area postrema in rats

Summary Acute surgical excision of the area postrema (AP) in the rat failed to affect arterial blood pressure or heart rate.There was no effect on cardiovascular reflex responses during diving or on the heart rate responses to acute decreases or increases of blood pressure caused by bradykinin or angiotensin, respectively. Electrolytic lesions of the AP in acute experiments caused variable damage to the nucleus tractus solitarii (NTS). In these rats large variations in blood pressure occurred. Excision of the AP in a chronic experiment failed to change blood pressure, heart rate, water intake or plasma renin activity. In contrast, bilateral electrolytic lesions of the NTS at the level of the AP caused a severe acute hypertension and completely blocked cardiovascular reflex responses. Hypertension also existed in rats with NTS lesions studied for a longer period of time.These experiments failed to confirm the hypothesis that the AP exerts a tonic inhibitory control of basal blood pressure. Hypertension previously reported after ablation of the AP may be explained by damage to the NTS.     

Cardiovascular activity during mental stress following vigorous exercise in sportsmen and inactive men

Thirty-six competitive sportsmen and 36 inactive men participated in a two-session experiment. Session 1 involved exercise to exhaustion so as to assess maximal oxygen consumption (V?o_{2 max}. In Session 2, both groups were randomized into three experimental conditions: 20 min of exercise at high intensity (70%V?o_{2 max}) or moderate intensity (50% V˙o_{2 max}) or a light exercise control. Following 30 min of recovery, all subjects performed mental arithmetic and public speech tasks in a counterbalanced order. Cardiovascular, electrodermal, respiratory, and subjective variables were recorded. Sportsmen had higher V˙o_{2 max}, lower body fat, and lower resting heart rate (HR) than inactive men. A postexercise hypotensive response was observed among subjects in the 70% and 50% V˙o_{2 max} conditions, accompanied by baroreceptor reflex inhibition in the 70% condition. Systolic pressure was lower during mental arithmetic and during recovery from the speech task in the high-intensity than in the control group. Diastolic pressure was lower following mental arithmetic in the high-intensity group. No differences in HR reactivity, electrodermal, or respiratory parameters were observed, but baroreceptor reflex sensitivity was inhibited during mental arithmetic. The results are discussed in relation to previous reports of suppressed cardiovascular reactivity to mental stress tests following vigorous exercise and the role of stress-related processes in the antihypertensive response to physical training.     

Localization and action of adenosine A2a receptors in regions of the brainstem important in cardiovascular control

In vitro autoradiography and central microinjections of a P1 adenosine A2a receptor antagonist have been employed to investigate a possible role for centrally located adenosine A2a receptors in modulation of the baroreceptor reflex. In vitro autoradiography using [125I]4-(2-[7-amino-2-[2-furyl][3,2,4]triazolol[2,3-a][1,3,5]tr iazin-5-yl-amino]ethyl)phenol ([125I]ZM241385), the high-affinity adenosine A2a receptor antagonist, revealed a heterogeneous distribution of adenosine A2a binding sites within the lower brainstem of the rat. Image analysis showed high levels of binding in rostral regions of both the nucleus tractus solitarius and the ventrolateral medulla. Intermediate levels of binding were observed in the commissural nucleus tractus solitarius and the dorsal vagal motor nucleus, with low levels of binding in caudal regions of the nucleus tractus solitarius and the ventrolateral medulla, and the hypoglossal nucleus. Unilateral microinjections of unlabelled ZM241385 into the nucleus tractus solitarius had no effect on baseline levels of arterial pressure, heart rate and phrenic nerve activity recorded in anaesthetized, artificially ventilated rats. However, microinjections of ZM241385 reduced the bradycardia evoked by stimulation of the ipsilateral aortic nerve. In contrast, ZM241385 had no effect on the depressor response or the reduction in phrenic nerve activity evoked by aortic nerve stimulation. Our results indicate that adenosine A2a binding sites are located in a number of brainstem regions involved in autonomic function, consistent with the idea that adenosine acts as a neuromodulator of a variety of cardiorespiratory reflexes. Specifically, the data support the hypothesis that adenosine A2a receptors located within the nucleus tractus solitarius are activated during baroreceptor stimulation and have an important modulatory role in the pattern of cardiovascular changes associated with this reflex.