Baroreceptor Input Research Articles

The Baroreflex And Beyond: Control Of Sympathetic Vasomotor Tone By Gabaergic Neurons In The Ventrolateral Medulla

1. Barosensitive, bulbospinal neurons in the rostral ventrolateral medulla (RVLM), which provide the major tonic excitatory drive to sympathetic vasomotor neurons, are prominently inhibited by GABA. 2. A major source of the GABAergic inhibition to presympathetic RVLM neurons arises from an area immediately caudal to the RVLM, known as the caudal ventrolateral medulla (CVLM). 3. Arterial baroreceptor afferents projecting to the nucleus tractus solitarius (NTS) provide a major tonic excitatory input to GABAergic CVLM neurons. These CVLM cells are a critical component for baroreflex-mediated changes in presympathetic RVLM neuronal activity, sympathetic nerve activity (SNA) and arterial pressure (AP). 4. Some GABAergic CVLM neurons are tonically activated by inputs independent of arterial baroreceptors or the NTS, providing a GABAergic-mediated inhibition of the presympathetic RVLM neurons that is autonomous of baroreceptor inputs. 5. GABAergic CVLM neurons appear to play two distinct, yet important, roles in the regulation of sympathetic vasomotor tone and AP. They dampen immediate changes in AP via the baroreflex and tonically inhibit the activity of the presympathetic RVLM neurons by baroreceptor-independent mechanisms. This baroreceptor-independent, GABAergic inhibition of presympathetic RVLM neurons may play an important role in determining the long-term level of sympathetic vasomotor tone and AP.

Caudal ventrolateral medulla mediates the depressor response elicited by the greater splanchnic nerve afferent stimulation in rats

Caudal ventrolateral medulla (CVLM) plays an important role in the regulation of reflex cardiovascular activity. In the present study, the possible involvement of the CVLM in mediating the depressor response elicited by the greater splanchnic nerve (GSPL) afferent stimulation was explored in rats anesthetized with urethane and alpha-chloralose. Microinjection of lidocaine, and the glutamate receptor antagonists, kynurenic acid and 2-amino-7-phosphonolieptanoic acid, into the CVLM significantly blocked the depressor response induced by the GSPL afferent stimulation. Electrical stimulation of the GSPL inputs excited 48 of 75 CVLM neurons tested (64%). Sixteen out of 21 excited CVLM neurons tested received baroreceptor inputs. Coherence analysis revealed a strong cardiac-related rhythm in the discharges of 11 out of these 21 excited neurons. These results suggest the involvement of CVLM neurons and activation of glutamate receptors in the CVLM in mediating the depressor response induced by the GSPL afferent stimulation in rats.

Chapter 25 Oxytocin, vasopressin and atrial natriuretic peptide control body fluid homeostasis by action on their receptors in brain, cardiovascular system and kidney

Publisher Summary This chapter presents a remarkable interaction of oxytocin (OT) and atrial natriuretic peptide (ANP) to control not only the intake of salt and water in actions mediated by sodium receptors and baroreceptors but also to control the release of natriuretic hormones from the brain, heart, and vascular system. In the brain, baroreceptor input and input from sodium receptors cause release of ANP, which in turn activates the release of OT. OT and ANP act to inhibit water and salt intake probably by inhibiting the intrahypothalamic release of angiotensin II, whereas the principal mechanism to release ANP from the heart is by OT's activation of its receptors on the heart, particularly in the fight atrium, to trigger the release of ANP. OT acts in the brain and kidney not only by releasing ANP but also by activating nitric acid synthase (NOS). All three transmitters act through cyclic guanosine 3'-5'-monophosphate (cGMP). The OT acts on its receptors to activate NOS causing a further increase in cGMP augmenting the natriuresis and kaliuresis so that the resulting effect is the combination of the increased cGMP induced by OT through NO and ANP by its own action to increase cGMP. The increased electrolyte excretion finally returns the blood volume and extracellular fluid volume to normal levels.

What does the brain know about blood pressure?

The integration of baroreceptor inputs within the central nervous system is modulated by a variety of inhibitory processes. It is proposed that, in hypertension, brain stem neurons adapt to increased excitatory baroreceptor inputs by increasing the efficacy of these inhibitory processes. Enhanced inhibition maintains some degree of reflex function in hypertension.

Role of the medulla oblongata in hypertension.

Brain pathways controlling arterial pressure are distributed throughout the neuraxis and are organized in topographically selective networks. In this brief review, we will focus on the medulla oblongata. The nucleus tractus solitarius (NTS) is the primary site of cardiorespiratory reflex integration. It is well accepted that lesions or other perturbations in the NTS can result in elevations of arterial pressure (AP), with many of the associated features so commonly found in humans. However, recent studies have shown 2 distinct subpopulations of neurons within the NTS that can influence AP in opposite ways. Commissural NTS neurons located on the midline may contribute to maintenance of hypertension in spontaneously hypertensive rats (SHR), because small lesions in this area result in a very significant reduction in AP. Also involved in this blood pressure regulation network are 2 distinct regions of the ventrolateral medulla: caudal (CVLM) and rostral (RVLM). Neurons in CVLM are thought to receive baroreceptor input and to relay rostrally to control the activity of the RVLM. Projections from CVLM to RVLM are inhibitory, and a lack of their activity may contribute to development of hypertension. The RVLM is critical to the tonic and reflexive regulation of AP. In different experimental models of hypertension, RVLM neurons receive significantly more excitatory inputs. This results in enhanced sympathetic neuronal activity, which is essential for the development and maintenance of the hypertension.

Exercise and Sensory Integration

Since NTS neurons receive synaptic input from many sensory modalities, it is crucial to understand the neuronal mechanisms involved in synaptic processing. We have proposed that GABA-containing neurons in the NTS are the primary target for somatic afferent fibers activated by skeletal muscle contraction. In our model, local inhibition of baroreceptor signaling is necessary to counteract the increase in baroreceptor input such that NTS output is normalized and baroreflex sensitivity is maintained during exercise. This GABAergic mechanism, in conjunction with sympathoexcitation evoked by somatic afferents, preserves reflex sensitivity and resets the baroreflex, respectively. Unfortunately, there is insufficient data to date to support or refute the proposed role for GABA on baroreflex function during exercise. However, we feel that this model will be useful in formulating future experiments to explore these synaptic interactions.

Response Properties of Baroreceptive NTS Neurons

Neurons in the nucleus of the solitary tract (NTS) responding to activation of arterial baroreceptors were recorded intracellularly using patch pipettes in an in situ arterially perfused working heart-brain stem preparation of rat. Seven of 15 (i.e., 46%) of NTS neurons showed adaptive (nonlinear) excitatory synaptic response patterns during baroreceptor stimulation followed by an "evoked hyperpolarization." This evoked hyperpolarization was stimulus intensity dependent and capable of shunting out a subsequent baroreceptor input. We suggest that this adaptive response behavior may be mediated, in part, by calcium-dependent potassium currents (IKCa) since neurons showed spike frequency adaptation during step depolarizations and an after-hyperpolarization after repetitive firing. Furthermore, in in vivo anesthetized rats, NTS microinjections of either charybdotoxin (225 fmol) or apamin (4.5 pmol) to block IKCa increased the baroreceptor reflex gain. Our data purport that the responsiveness of baroreceptive NTS neurons can be regulated by intrinsic membrane conductances such as IKCa. Modulation of such conductances during either physiological (exercise) or pathophysiological (essential hypertension) conditions may lead to changes in both the operating point and gain of the baroreceptor reflex.

Regulation of sympathetic nervous system function after cardiovascular deconditioning.

Humans subjected to prolonged periods of bed rest or microgravity undergo deconditioning of the cardiovascular system, characterized by resting tachycardia, reduced exercise capability, and a predisposition for orthostatic intolerance. These changes in cardiovascular function are likely due to a combination of factors, including changes in control of body fluid balance or cardiac alterations resulting in inadequate maintenance of stroke volume, altered arterial or venous vascular function, reduced activation of cardiovascular hormones, and diminished autonomic reflex function. There is evidence indicating a role for each of these mechanisms. Diminished reflex activation of the sympathetic nervous system and subsequent vasoconstriction appear to play an important role. Studies utilizing the hindlimb-unloaded (HU) rat, an animal model of deconditioning, evaluated the potential role of altered arterial baroreflex control of the sympathetic nervous system. These studies indicate that HU results in blunted baroreflex-mediated activation of both renal and lumbar sympathetic nerve activity in response to a hypotensive stimulus. HU rats are less able to maintain arterial pressure during hemorrhage, suggesting that diminished ability to increase sympathetic activity has functional consequences for the animal. Reflex control of vasopressin secretion appears to be enhanced following HU. Blunted baroreflex-mediated sympathoexcitation appears to involve altered central nervous system function. Baroreceptor afferent activity in response to changes in arterial pressure is unaltered in HU rats. However, increases in efferent sympathetic nerve activity for a given decrease in afferent input are blunted after HU. This altered central nervous system processing of baroreceptor inputs appears to involve an effect at the rostral ventrolateral medulla (RVLM). Specifically, it appears that tonic GABAA-mediated inhibition of the RVLM is enhanced after HU. Augmented inhibition apparently arises from sources other than the caudal ventrolateral medulla. If similar alterations in control of the sympathetic nervous system occur in humans in response to cardiovascular deconditioning, it is likely that they play an important role in the observed tendency for orthostatic intolerance. Combined with potential changes in vascular function, cardiac function, and hypovolemia, the predisposition for orthostatic intolerance following cardiovascular deconditioning would be markedly enhanced by blunted ability to reflexly activate the sympathetic nervous system.

Properties of NTS neurons receiving input from barosensitive receptors.

Afferent input from barosensitive receptors, including carotid baroreceptors and cardiac mechanoreceptors, has been found to produce different types of discharge patterns in neurons in the nucleus tractus solitarius (NTS). The discharge patterns of the neurons may be dependent on many factors, including input from the different barosensitive receptor subtypes, the contribution of different ionotropic glutamate receptors [NMDA (N-methyl-D-aspartate) versus nonNMDA receptors] in transmission of the input, effects of different neuropeptide neurotransmitters/neuromodulators on afferent transmission, or the order of the neuron within the barosensitive reflex arc. It is not clear if the roles of the glutamate receptor subtypes are the same for neurons activated by the different barosensitive inputs. In addition, the amount of afferent input from the barosensitive receptors, due to increases or decreases in stimulating pressures, may result in altering the roles of the ionotropic glutamate receptor subtypes. While most evidence suggests that nonNMDA receptors play the greatest role in the transmission of afferent activity to second-orders NTS neurons, it is possible that increases in afferent input may lead to an enhanced role for NMDA receptors in the transmission of the barosensitive input, since increased depolarization of the NTS neurons may lead to removal of a Mg2+ block of the NMDA channel. Transmission of baroreceptor input at third- and higher-order neurons has been found to involve both nonNMDA and NMDA receptors, suggesting a possible functional role for the distribution of these receptor types. The roles of these different factors in the initiation of NTS neuronal discharge will be discussed.

Attenuation of the afferent limb of the baroreceptor reflex in streptozotocin-induced diabetic rats

Diabetic autonomic neuropathy is a common complication following prolonged diabetes. Alterations of cardiovascular reflexes contribute to the increased cardiovascular morbidity and mortality seen in diabetic patients. This study sought to better characterize these complications by investigating the afferent limb of the baroreceptor reflex in an experimental rat model of diabetes. Streptozotocin (STZ)-induced diabetic and euglycemic control rats were studied at 8- and 16-week time points after initiation of the experiment. Activation of the afferent limb of the baroreceptor reflex was assessed by measuring the numbers of c-Fos-immunoreactive (ir) neurons in the CNS site of termination of the baroreceptor afferent neurons, the nucleus of the solitary tract (NTS). Initial experiments established that baseline cardiovascular parameters and NTS expression of c-Fos-ir neurons were not different between diabetic and control rats at either time point. Phenylephrine (PE)-induced activation of baroreceptors resulted in a significant elevation in the numbers of c-Fos-ir neurons in the NTS of control rats. Although diabetic rats showed similar pressor responses to PE, the activation of c-Fos-ir neurons in the NTS of diabetic rats was significantly attenuated. At both 8 and 16 weeks, STZ-induced diabetic rats had significantly fewer c-Fos-ir neurons in the commissural NTS and in the caudal subpostremal NTS when compared to the non-diabetic control animals receiving PE. These data suggest that STZ-induced diabetes, for a period of 8 and 16 weeks, results in reduced activity in the afferent baroreceptor input to the NTS, and are consistent with diabetes-induced damage to baroreceptor afferent nerves.

The discharge of a subset of serotonergic raphe magnus cells is influenced by baroreceptor input

In order to determine whether serotonergic cells in the medullary raphe magnus (RM) receive baroreceptor input, cells were tested for their responses to descending aortic occlusion, aortic nerve stimulation, or systemic phenylephrine administration in the lightly anesthetized rat. Serotonergic cells were identified physiologically by a quantitative analysis of their slow and steady discharge. Greater than 40% of the serotonergic RM cells tested responded to brief occlusion of the descending aorta at the level of the coeliac arteries, a stimulus that elevated blood pressure by about 30 mmHg. Similarly, about 40% of the serotonergic RM cells responded to stimulation of the aortic nerve, a nerve that contains primarily baroreceptor afferents from the aortic arch. Greater than 70% of RM serotonergic cells responded to phenylephrine administration which elevated blood pressure by an average of 50 mmHg. Serotonergic cell responses to all methods of baroreceptor activation were small in magnitude and were largely restricted in time to the stimulus duration. The results indicate that a subset of serotonergic cells in RM are influenced by baroreceptor activity.

Cardiac vagal and sympathetic efferent discharges are differentially modified by stretch of skeletal muscle.

We directly measured cardiac vagal efferent nerve activity (CVNA) and cardiac sympathetic efferent nerve activity (CSNA) in cats decerebrated at the level of the precollicular-premammillary body while the hindlimb or the triceps surae muscle was passively stretched. CVNA gradually decreased during passive stretch of the hindlimb, and this decrease was sustained throughout the stretch. CSNA increased at the onset of passive stretch, but this increase was not sustained. CVNA and CSNA responded differentially to graded passive stretches of the triceps surae muscle as well as the hindlimb. The sustained decrease in CVNA but not the initial increase in CSNA became greater depending on muscle length and developed tension. The time course and direction of the cardiac autonomic responses to muscle stretch were not affected by partial sinoaortic denervation, although the magnitude of the CSNA response was augmented. We conclude that the muscle mechanoreflex contributes to differential regulation of cardiac parasympathetic and sympathetic efferent discharges during passive stretch of skeletal muscle irrespective of arterial baroreceptor input.

Discharge pattern of renal sympathetic nerve activity in the conscious rat: spectral analysis of integrated activity.

We investigated the periodic characteristics of bursting discharge in renal sympathetic nerve activity (RSNA) in conscious rats. Employing a discrete fast Fourier transform algorithm, a power spectrum analysis was used to quantify periodicities present in rectified and integrated RSNA whose signal-to-noise ratio in the recordings was greater than six. In conscious rats with intact baroreceptors, RSNA was characterized by four frequency components occurring at about 0.5, 1.5, 6, and 12 Hz, which corresponded to the low-frequency fluctuation of heart rate, respiration, and frequency of heart beat, and its harmonics, respectively. After intravenous infusion of sodium nitroprusside (SNP) to elicit reflex increases in RSNA and heart rate, the power for the component at 6 Hz followed the changes in heart beat frequency and was significantly increased, while those for the three other components were attenuated or experienced no change. In sino-aortic denervated (SAD) conscious rats, all four components were abolished, and the power spectrum was well fitted by a flat or Lorentzian curve, suggesting an almost random pattern. Only a respiratory-related component, which suggested common central modulation, appeared sporadically for short periods but was absent for the most part. Therefore most of this component together with the low-frequency component was also likely due to the baroreceptor-dependent peripheral modulation. The activity was sorted in 15 subgroups on the basis of spike amplitudes in the RSNA. Each subgroup showed frequency characteristics similar to the whole nerve activity. These results suggest that all periodicity in the RSNA of conscious rats with intact baroreceptors is caused by the baroreceptor input.

Responses of aortic depressor nerve-evoked neurones in rat nucleus of the solitary tract to changes in blood pressure.

Using electrophysiological techniques, the discharge of neurones in the nucleus of the solitary tract (NTS) receiving aortic depressor nerve (ADN) inputs was examined during blood pressure changes induced by I.V. phenylephrine or nitroprusside in anaesthetized, paralysed and artificially ventilated rats. Various changes in discharge rate were observed during phenylephrine-induced blood pressure elevations: an increase (n = 38), a decrease (n = 5), an increase followed by a decrease (n = 4) and no response (n = 11). In cells receiving a monosynaptic ADN input (MSNs), the peak discharge frequency response was correlated to the rate of increase in mean arterial pressure (P < 0.01) but was not correlated to the absolute increase in blood pressure. The peak discharge frequency response of cells receiving a polysynaptic ADN input (PSNs) was correlated to neither the absolute increase in blood pressure nor the rate of increase in mean arterial pressure. Diverse changes in discharge rate were observed during nitroprusside-induced reductions in blood pressure: an increase (n = 3), a decrease (n = 10), an increase followed by a decrease (n = 3) and no response (n = 6). Reductions in pressure of 64 +/- 2 mmHg produced weak reductions in spontaneous discharge of 1.3 +/- 0.9 Hz and only totally abolished spontaneous discharge in one neurone. These response patterns of NTS neurones during changes in arterial pressure suggest that baroreceptor inputs are integrated differently in MSNs compared to PSNs. The sensitivity of MSNs to the rate of change of pressure provides a mechanism for the rapid regulation of cardiovascular function. The lack of sensitivity to the mean level of a pressure increase in both MSNs and PSNs suggests that steady-state changes in pressure are encoded by the number of active neurones and not graded changes in the discharge of individual neurones. Both MSNs and PSNs receive tonic excitatory inputs from the arterial baroreceptors; however, these tonic inputs appear to be insufficient to totally account for their spontaneous discharge.

C-Fos expression in the midbrain periaqueductal gray during static muscle contraction.

The periaqueductal gray (PAG) of the midbrain is involved in the autonomic regulation of the cardiovascular system. The purpose of this study was to determine if static contraction of the skeletal muscle, which increases arterial blood pressure and heart rate, activates neuronal cells in the PAG by examining Fos-like immunoreactivity (FLI). Muscle contraction was induced by electrical stimulation of the L7 and S1 ventral roots of the spinal cord in anesthetized cats. An intravenous infusion of phenylephrine (PE) was used to selectively activate arterial baroreceptors. Extensive FLI was observed within the ventromedial region (VM) of the rostral PAG, the dorsolateral (DL), lateral (L), and ventrolateral (VL) regions of the middle and caudal PAG in barointact animals with muscle contractions, and in barointact animals with PE infusion. However, muscle contraction caused a lesser number of FLI in the VM region of the rostral PAG, the DL, L, and VL regions of the middle PAG and the L and VL regions of the caudal PAG after barodenervation compared with barointact animals. Additionally, the number of FLI in the DL and L regions of the middle PAG was greater in barodenervated animals with muscle contraction than in barodenervated control animals. Thus these results indicated that both muscle receptor and baroreceptor afferent inputs activate neuronal cells in regions of the PAG during muscle contraction. Furthermore, afferents from skeletal muscle activate neurons in specific regions of the PAG independent of arterial baroreceptor input. Therefore, neuronal cells in the PAG may play a role in determining the cardiovascular responses during the exercise pressor reflex.

Partial spectral analysis of cardiac-related sympathetic nerve discharge.

We have studied the relationship between pulse synchronous baroreceptor input (represented by the arterial pulse, AP) and the cardiac-related rhythm in sympathetic nerve discharge (SND) of urethan-anesthetized cats by using partial autospectral and partial coherence analysis. Partial autospectral analysis was used to mathematically remove the portion of SND that can be directly attributed to the AP, while partial coherence analysis was used to removed the portion of the relationship between the discharges of sympathetic nerve pairs that can be attributed to linear AP-SND relationships that are common to the nerves. The ordinary autospectrum of SND (AS(SND)) and coherence functions relating the discharges of nerve pairs (Coh(SND-SND)) contained a peak at the frequency of the heart beat. When the predominant mode of coordination between AP and SND was a phase walk, partialization of the autospectra of SND with AP (AS(SND/AP)) left considerable power in the cardiac-related band. In contrast, when the predominant mode of coordination between AP and SND was phase-locking, there was virtually no cardiac-related activity remaining in AS(SND/AP). Partialization of Coh(SND-SND) with AP reduced the peak coherence within the cardiac-related band in both modes of coordination but to a much greater extent during phase-locking. After baroreceptor denervation, Coh(SND-SND) at the cardiac frequency remained significant, although a clear peak above background coherence was no longer apparent. These results are consistent with a model in which the central circuits controlling different sympathetic nerves share baroreceptor inputs and in addition are physically interconnected. The baroreceptor-sympathetic relationship contains both linear and nonlinear components, the former reflected by phase-locking and the latter by phase walk. The residual power in AS(SND/AP) during phase walk can be attributed to the nonlinear relationship, and the residual peak in partialized nerve-to-nerve coherence (Coh(SND-SND/AP)) arises largely from nonlinearities that are common to the two nerves. During both phase walk and phase-locking, in addition to common nonlinear AP-SND relationships, coupling of the central circuits generating the nerve activities may contribute to Coh(SND-SND/AP) because significant Coh(SND-SND) was still observed following baroreceptor denervation.

Effect of pulmonary C-fibre afferent stimulation on cardiac vagal neurones in the nucleus ambiguus in anaesthetized cats.

It has been demonstrated previously that the vagal bradycardia evoked by activation of pulmonary C-fibres is not respiratory modulated. Experiments were carried out in alpha-chloralose anaesthetized cats to determine if these cardiac vagal preganglionic neurones (CVPNs) in the nucleus ambiguus (NA), which have respiratory modulated activity, can be activated when pulmonary C-fibre afferents are stimulated by right atrial injections of phenylbiguanide (PBG). Eleven CVPNs with B-fibre axons in the right cardiac vagal branches were identified and found to be localized within or ventrolateral to the nucleus ambiguus. Ionophoretic application of a high current of dl-homocysteic acid (DLH) induced a vagally mediated bradycardia and hypotension in six of eight sites from which CVPNs were recorded. The activity of B-fibre CVPNs, whether spontaneous (n = 4) or induced by ionophoresis of DLH (n = 7) was respiratory modulated, firing perferentially during post-inspiration and stage 2 expiration. This activity also correlated with the rising phase of the arterial blood pressure wave consistent with these CVPNs receiving an arterial baroreceptor input. Right atrial injections of PBG excited nine of eleven CVPNs tested. In eight of these activated neurones the onset latency of the excitation was within the pulmonary circulation time, consistent with being activated only by pulmonary C-fibre afferents. In two neurones the PBG-evoked excitation still occurred when central inspiratory drive was inhibited, as indicated by the disappearance of phrenic nerve activity. In conclusion, B-fibre respiratory modulated CVPNs can be activated following stimulation of pulmonary C-fibre afferents.

The renal effects of corticotropin releasing hormone: implication of vasopressin and atrial natriuretic peptide

To evaluate the hypothesized renal actions of corticotropin releasing hormone (CRH), adult male conscious normally hydrated or volume-expanded rats (6 ml saline) were injected iv with various doses of CRH (1–5 μg). Some groups of rats were injected with arginine vasopressin (AVP) antagonist (2 or 10 μg) iv prior to CRH (5 μg). Urine was collected for volume, Na, K, and cyclic guanosine monophosphate (cGMP) determination. AVP and atrial natriuretic pepride (ANP) were determined in blood by radioimmunoassay. Blood pressure (BP) was measured by telemetry. In both normally hydrated and volume expanded conscious rats, the biphasic effects of CRH injected iv were observed. Initially, within the first hour, CRH caused dose-dependent antidiuresis, decreased sodium, potassium and urinary cGMP excretion. Plasma AVP was already increased significantly (p < 0.01) within 5 min after injection from 3.9 ± 0.5 pg/ml to 15.5 ± 3.3 pg/ml (n = 15) at 15 min, then declined by 30 min to the concentration reached at 5 min and was maintained for 180 min. Changes in plasma ANP followed a mirror image of AVP. Plasma ANP correlated with the decrease of ANP synthesis in the left ventricle. Four hours after the injection, a marked diuresis, natriuresis, kaliuresis and an increase in urinary cGMP occurred. This was accompanied by increased ANP mRNA in the right atrium at 180 min. All urinary changes were reversed by a V2 receptor antagonist (2 or 10 μg) given iv. Control injection of saline evoked an immediate (3–5 min) increase in BP, and this elevation was markedly inhibited by CRH (5 μg). Heart rate was further increased. We hypothesize that the renal effects are mediated by vasodilation induced by CRH that decreases the baroreceptor input to the brain, leading to the rapid release of AVP which acts on the heart and inhibits ANP release and synthesis. These effects could be of physiological significance during the stress.

Cardiovascular responses to carotid chemoreceptor stimulation in the dog: their modulation by urinary bladder distension.

Respiratory, heart rate and hindlimb vascular responses were studied in response to increasing levels of stimulation of the carotid body chemoreceptors, together with an examination of the modulation of their effects by distension of the urinary bladder in the dog anaesthetized with a mixture of chloralose and urethane. The vascularly isolated carotid bifurcation regions were perfused with blood, stimulation of the carotid bodies being carried out by three different levels of hypoxic isocapnic blood (PO2 approximately 58, 40 and 22 mmHg) obtained from a donor animal. A vascularly isolated hindlimb was autoperfused at constant blood flow through its femoral artery. In spontaneously breathing animals, increasingly intense hypoxic stimulation of the carotid bodies caused a progressive augmentation of respiratory minute volume. Superimposition of distension of the bladder increased ventilation further, by the same amount during hypoxic as during normoxic blood perfusion of the chemoreceptors. Prevention of the effects of lung stretch afferent stimulation by artificial ventilation modified the heart rate and hindlimb vascular responses to excitation of the carotid bodies by revealing or accentuating the primary cardiovascular responses, bradycardia and vasoconstriction. In contrast, no such respiratory modulation was apparent in the cardiovascular responses to bladder distension. When, under conditions of artificial ventilation and in the absence of changes in the arterial baroreceptor input, the primary cardio-inhibitory and vasoconstrictor responses to carotid chemoreceptor stimulation predominated, the heart slowed progressively as the stimulus was increased. At the same time the cardio-accelerator effects of bladder distension progressively diminished, indicating an interaction between the cardiac reflex responses evoked by the two inputs. In contrast, the reflex vascular responses resulting from stimulation of the two inputs were additive, at least for PO2 levels of carotid body perfusate down to approximately 40 mmHg. In conclusion these experiments demonstrate the differential nature of the integration of respiratory and cardiovascular responses evoked by stimulation of the carotid chemoreceptors and bladder distension.

Baroreceptive and somatosensory convergent thalamic neurons project to the posterior insular cortex in the rat

Connectivity between the rat posterior insula and the ventrobasal thalamus has been demonstrated anatomically. Neurons convergent for baroreceptor and nociceptive input have also been identified in the homologous anterior insula of the primate. Whether similar convergent cells exist in the ventrobasal thalamus was investigated in 30 urethane anesthetized male Sprague–Dawley rats. Six classes of cells were identified in the right ventrobasal thalamus: (a) 83/159 (52%) baroreceptive and nociceptive convergent units; (b) 2/159 (1%) convergent cells responding to baroreceptor activation and light touch; (c) 44/159 (28%) purely nociceptive units; (d)10/159 (6%) purely baroreceptive units; (e) 1/159 (0.6%) cells responding to brush alone and (f) 19/159 (12%) unresponsive units. Of the viscerosomatic convergent cells, 66/85 (78%) were situated in the ventroposterolateral nucleus (VPL), 6/85 (7%) in the ventroposterolateral parvicellular nucleus (VPLpc), and 13/85 (15%) in the ventroposteromedial nucleus (VPM). Fifteen right ventrobasal thalamic units were antidromically activated and 34 units orthodromically activated by right posterior insular microstimulation. Cobalt injection into the right ventrobasal thalamus blocked the right insular response to baroreceptor activation by >70%. These data indicate: (a) baroreceptive and somatosensory nociceptive convergent units exist in the ventrobasal thalamus; (b) thalamic convergent neurons project directly to the ipsilateral posterior insula and receive reciprocal insulothalamic projections; and (c) a significant proportion of baroreceptor input relays to the posterior insula through the ipsilateral ventrobasal thalamus.