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In 65 cats anesthetized with chloralose (40 mg/kg) and urethane (400 mg/kg), the effects of electrical stimulation and microinjection of sodium glutamate (0.25 M, 100–200 nl) in the pressor areas in the rostral brain stem on the evoked L5 ventral root response (EVRR) due to intermittent stimulation of sciatic afferents were compared to stimulating the dorsomedial (DM) and ventrolateral (VLM) medulla. In general, stimulating these rostral brain stem pressor areas including the diencephalon (DIG) and rostral pons (RP) produced increases in systemic arterial pressure (SAP). In most of the cases (85%) there were associated changes in the EVRR, predominantly a decrease in EVRR (72%). Stimulation of the midbrain (MB, principally in the periaqueductal grey) produced decreases in SAP and EVRR. Decreases in EVRR was observed in 91% of the DM and VLM stimulations in which an increase in SAP was produced. This EVRR inhibition was essentially unaltered after acute midcollicular decerebration. Increases in EVRR were also observed and occurred more often in the rostral brain stem than in the medulla. Since changes of both EVRR and SAP could be reproduced by microinjection of Glu into the cardiovascular-reactive areas of the brain stem, this suggests that neuronal perikarya in these areas are responsible for both actions. On some occasions, Glu induced changes in EVRR but not in SAP. This effect occurred more frequently in the rostral brain stem than in the medulla. The present data suggest that separate neuron population exist in the brain stem for the integration of SAP and spinal reflexes. These neurons are relatively dispersed from DIC to RP but are in close proximity to one another in the medulla. Rostral structures also contain more neurons responsible for augmenting spinal reflexes.

In 65 cats anesthetized with alpha-chloralose and urethane, the effects of insulin on cardiovascular responses to stimulation of various structures in the brain stem were studied. The threshold dose of insulin injected intravenously that produced systemic hypoglycemia was 5-10 U/kg. Subthreshold hypoglycemic doses of insulin were used intracerebroventricularly (0.25 U/kg) or intracerebrally (2 mU in 200 nl). Sixty minutes after intravenous insulin, when serum glucose concentrations decreased from 158 to 43 mg/100 ml, pressor responses to stimulation of the periaqueductal gray of midbrain (PAG), locus coeruleus (LC), dorsal medulla (DM), ventrolateral medulla (VLM), and parvocellular reticular nucleus (PVC) decreased significantly. Depressor and bradycardiac response to stimulation of paramedian reticular nucleus or dorsal motor nucleus of vagus (DMV) decreased significantly as well. Thirty minutes after intracerebroventricular insulin, pressor responses of PAG, DM, and the bradycardiac response of DMV decreased significantly. Thirty minutes after intracerebral insulin, pressor responses and renal nerve activities of LC (but not PAG), VLM, DM, and PVC decreased significantly. A similar but faster onset (5 min) of depression of cardiovascular responses on stimulating the LC, VLM, DM, and PVC was observed in another six acutely midcollicular-decerebrate cats recovered from halothane anesthesia. These findings suggest that insulin directly inhibits the vasomotor structures of the brain stem and decreases the pressor responses to stimulation.

To investigate the interaction between cardiovascular (CV)-reactive areas in the brain stem and urinary bladder (UB) motility, 48 adult cats of either sex were anesthetized intraperitoneally with alpha-chloralose (40 mg/kg) and urethan (400 mg/kg). The changes of UB motility and systemic arterial blood pressure (SAP) were produced by microinjection of sodium glutamate (0.5 M, 100-200 nl) into the pressor, depressor, or vagobradycardiac areas of the brain stem. Stimulation of these CV-reactive areas increased or decreased UB motility. Areas that produced an increase in UB motility listed in decreasing order of effectiveness are locus ceruleus-parabrachial nucleus in the pons, dorsal medulla, dorsal motor nucleus of vagus, and ventrolateral medulla. Areas eliciting a decrease in UB motility listed in decreasing order are gigantocellular tegmental field, parvocellular reticular nucleus, and ambiguus nucleus. Stimulation of other pressor sites in medulla also increased UB motility. Activation of the paramedian reticular nucleus, which consistently produced depressor responses, and activation of raphe nuclei, which produced depressor or pressor responses, consistently decreased UB motility. The integrity of the vagus nerve was not essential for the UB response to brain stimulation. These findings indicate that neuronal mechanisms for controlling UB and CV functions coexist at many sites in the brain stem. At those sites that commonly produce changes in UB motility, the type of UB response (excitation or inhibition) was in the same direction as the change of SAP. However, at some sites responses were inverse. It is not known whether the responses of the UB and CV system are controlled by common or separate populations of neurons at these sites.

SUMMARY 1. The inhibitory effects produced by activation of the medial region of caudal medulla on activities of the left and right cardiac sympathetic, vagus and greater splanchnic nerves were studied in chloralose-urethane anaesthetized cats. 2. Electrical stimulation of the medial region produced an 80–92% inhibition of the sympathetic nerve activities, and a 45% and 58% inhibition of the left and right cardiac vagal nerve activities, respectively. There were no significant differences between effects elicited in the left and right autonomic nerves. Similar but smaller inhibitory effects were produced by micro-injection of sodium glutamate (0.5 mol/L) or DL-homocysteic acid (50 mmol/L) to the same medullary sites. 3. These data suggest that neurons residing in the medial medullary region exert strong inhibitory effects on autonomic nerve activities. Since the vasculature is principally innervated by sympathetic nerves, inhibition of sympathetic nerve activities might be the principal factor responsible for the depressor effects caused by activation of the medial region of caudal medulla. The heart is innervated both by sympathetic and parasympathetic nerves. Thus, their simultaneous inhibition during activation of the medial region elicits only a weak and variable inhibition of the heart.

A stimulation of the gigantocellular tegmental field (FTG) in the medulla oblongata often increases systemic arterial blood pressure (SAP) and decreases heart rate (HR). We investigated if the cardioinhibitory/depressor areas, including the nucleus ambiguus (NA), the dorsal motor nucleus of vagus (DMV) and the caudal ventrolateral medulla (CVLM), underlied the functional expression of FTG neurons in regulating cardiovascular responses. In 73 chloralose-urethane anesthetized cats, the HR, SAP and vertebral nerve activity (VNA) were recorded. Neurons in the FTG, NA, DMV and CVLM were stimulated by microinjection of sodium glutamate (25 mM Glu, 70 nl). To study if the NA, DMV, and CVLM relayed the cardioinhibitory messages from the FTG, 24 mM kainic acid (KA, 100 nl) was used as an excitotoxic agent to lesion neurons in the NA, DMV or CVLM. We found that the cardioinhibition induced by FTG stimulation was significantly reduced by KA lesioning of the ipsilateral NA or DMV. Subsequently, a bilateral KA lesion of NA or DMV abolished the cardioinhibitory responses of FTG. Compared to the consequence of KA lesion of the DMV, only a smaller bradycardia was induced by FTG stimulation after KA lesion of the NA. The pressor response induced by Glu stimulation of the FTG was reduced by the KA lesion of the CVLM. Such an effect was dominant ipsilaterally. Our findings suggested that both NA and DMV mediated the cardioinhibitory responses of FTG. The pressor message from the FTG neurons might be partly working via a disinhibitory mechanism through the depressor neurons located in the CVLM.

1. Cats were anaesthetized with urethane (1100-1200 mg/kg, i.p.), supplemented with halothane inhalation during surgery. Responses in terms of systemic arterial pressure, mean systemic arterial pressure(MSAP), heart rate, mean blood flow of the common carotid artery and femoral artery, amplitude and frequency of vocalizations, thoracic-abdominal contractions and limb movements were recorded. 2. Microinjection of N-methyl-D-aspartate (NMDA; 20 mmol/L, 200 nL) into the pretentorial periaqueductal grey (PAG) produced two classes of response: (i) cardiovascular responses and vocalization; and (ii) cardiovascular responses without vocalization. 3. For class 1 responses, five types of vocalization concomitant with pressor (VPR) or depressor (VDPR) responses were observed: (i) type 1 VDPR and VPR, elicited in the rostral and caudal part of the dorsal PAG, produced vocalization of slight hissing, with or without limb movement, moderately increased flow of the common carotid and slightly increased flow of the femoral arteries; (ii) types 2 and 3 VPR, elicited in the dorsolateral and intermediate-lateral PAG, produced hissing-howling and growling, increased respiratory movement, with or without repetitive burst limb movements or stretching of paws, slightly decreased common carotid artery flow and inconsistent changes (increased or decreased slightly) in femoral artery flow; (iii) type 4 VPR, elicited in the dorsomedial and intermediate-medial PAG, produced meowing-crying but without limb movements, common carotid artery flow was increased, but the femoral artery flow was slightly decreased or increased markedly; and (iv) type 5 VPR, elicited in the ventromedial PAG, produced meowing-screaming with or without limb movements, common carotid artery flow increased moderately and femoral artery flow increased markedly. Vocalization was loud and wild in type 4 and 5 responses. 4. For class 2 responses, two types of responses were observed: (i) a pressor response (PR) alone, elicited in the dorsolateral and intermediate-lateral PAG, produced inconsistent changes in common carotid and femoral artery flow, which increased, decreased or underwent no change; and (ii) a depressor response (DPR) elicited in the ventrolateral PAG produced moderate increases of common carotid and femoral artery flow. 5. The reduction of resistance in the femoral artery was more prominent (P < 0.05) in type 1 VDPR than in DPR. Similar changes occurred in the femoral artery among types 3 (P < 0.05) and 5 VPR (P < 0.005) and PR. In addition, the frequency of vocalization was significantly positively correlated with the increase in MSAP (P < 0.05) and mean common carotid and femoral artery flow (both P < 0.01) in all types of VPR. 6. These results suggest the presence of neurons involved in the expression of defence reactions in a longitudinal, complicated functional organization in the entire PAG column. In particular, NMDA stimulation of the medial, dorsal and dorsolateral PAG may elicit five different types of defence reactions, expressed by various forms of cardiovascular alterations concomitant with vocalization responses.

The aim of the present study was to examine the relationship between the lateral tegmental field (FTL), a cardioinhibitory area, with other cardioinhibitory areas, i.e., the ambiguus nucleus (NA) and the dorsal motor nucleus of vagus (DMV) and the caudal ventrolateral medulla (CVLM), a vasopressor inhibitory area. In 55 cats anesthetized with chloralose (40 mg/kg) and urethane (400 mg/kg), the cardiovascular responses of heart rate (HR), systemic arterial blood pressure (SAP) and vertebral nerve activity (VNA) were recorded. The FTL, NA, DMV and CVLM were identified first by stimulation (rectangular pulses in 80 Hz, 0.5 ms, 50-100 microA) and then confirmed by microinjection of sodium glutamate (Glu, 0.25M, 70 nl). In studying the influence of NA, DMV, or CVLM lesion on the Gluinduced responses in FTL, kainic acid (KA, 24 mM, 100 nl) was microinjected into the NA, DMV or CVLM. FTL stimulation produced an average decrease of HR by 55%. After KA lesioning of the ipsilateral NA or the DMV, the decreased HR induced by FTL was significantly diminished. After subsequent lesion of the contralateral DMV or NA, the bradycardia of FTL was abolished. The reduction of resting HR was more intense after lesioning the NA than DMV and with the left side more than that of the right side. These studies suggest that the cardioinhibitory responses of FTL are mediated through both NA and DMV with predominance of the former, while the hypotensive effect of FTL is mediated through CVLM. The precise pathway responsible for the FTL-induced bradycardia and hypotension is to be determined.

Nitric oxide (NO) is involved in cardiovascular regulation and sympathetic nerve activity of the central nervous system (CNS). The nucleus tractus solitarius (NTS) is important to cardiovascular regulation. However, the physiological role of NO in cardiovascular regulation effecting through the NTS remains unclear. The purpose of this study is to investigate the effect of NO measured by in vivo voltammetry on the cardiovascular responses in NTS induced by N-methyl-D-aspartate (NMDA) in anesthetized cats. Extracellular NO concentration was monitored through a Nafion- and porphyrin-coated carbon fiber electrode, which has previously been demonstrated sensitive and selective to NO responses. Microinjection of NMDA into NTS elicited a dose-dependent decrease in cardiovascular responses associated with NO release. Following the dose-response curve, a dose of 3 nmol of NMDA was selected. Microinjection of NMDA into NTS produced depressor responses and NO release. These responses in NTS to NMDA were attenuated by pretreatment with a competitive antagonist, 2-amino-5-phosphonopentanoat (AP-5, 1 nmol), and methylene blue (MB, 1 nmol), an inhibitor of guanylate cyclase. These results suggest that NO is formed from NMDA activation in NTS and that NO diffuses out of neurons into the nearby target neurons to produce depressor response and NO release through cyclic guanosine monophosphate (cGMP) formation. In conclusion, NO mediates depressor response consequent to activation of NMDA receptors in neurons of NTS.

In this study, we developed a differential integrator unit containing a window discriminator (WPI-121) and three integrators (sample/hold, Gould) to characterize the difference in spikes involved in sympathetic vertebral nerve activity (VNA) and integrated VNA (Int. VNA) during stimulation of the dorsomedial (DM) and rostral ventrolateral (RVLM) medullar. The upper level (UL) in the window discriminator was set at a value, 80% of the VNA amplitude above the zero. The low level (LL) was set at a value 10% above the zero. The number of VNA spikes above the UL in the window discriminator was defined as Fa, while the number of VNA spikes within the UL and LL as Fw. In 26 cats anesthetized with urethane and alpha-chloralose, results showed that electrical stimulation and microinjections of glutamate (Glu, 0.25 M, 50 nl) or glycine (Gly, 1.0 M, 50 nl) at the same point in DM or RVLM increased both systemic arterial pressure (SAP) and Int. VNA. However, the increase of Int.VNA on DM stimulation was contributed by increases of both Fa and Fw, while on RVLM stimulation the increase of Int.VNA was mainly contributed by the increase of Fa, against a decrease of Fw. As compared to Glu, stimulation of DM by Gly produced more increase in Fw, while stimulation of RVLM by Gly produced more decrease in Fw. During RVLM stimulation the VNA was usually transferred to a huge synchronized oscillation. These findings suggest that although stimulations of the sympathetic-pressor neurons in DM and RVLM produce similar increases in SAP and VNA, the nature of these neurons is different.

Descending pathways of the pressor areas in dorsomedial (DM) and ventrolateral (VLM) medulla were studied physiologically and anatomically. The electrically induced pressor response from either DM or VLM that previously responded to glutamate (Glu) was slightly but not significantly decreased after splitting the medulla at midline. After electrolytic lesion in the ipsilateral lateral tegmental field (LTF) of caudal medulla, 4 mm caudal to the obex, electrically induced pressor responses from DM and VLM previously responded to Glu decreased significantly from 71% to 20% and from 57% to 7%, respectively. The dorsomedial LTF was found to be responsible for the DM responses, while the ventrolateral LTF for the VLM responses. Following electrolytic lesion in the ipsilateral dorsolateral funiculus (DLF) between C4 and C5, the magnitude of DM-induced pressor responses decreased significantly from 74% to 37% and that of the VLM from 75% to 14%. After electrolytic lesion at the ipsilateral intermediolateral cell column (IML) of T2 spinal cord, the pressor responses on DM and VLM stimulations also decreased significantly. Lesioning the remaining IML almost completely abolished the induced pressor responses. Seven to ten days following kainic acid injections into DM or VLM to destroy neurons therein, degenerative fibers (silver impregnation) were found to descend from the medulla to thoracic spinal cord, principally ipsilaterally, but with some fibers crossing to the controlateral medulla. Data from both physiological and anatomical studies suggest that fibers from DM and VLM descend ipsilaterally through different pathways and converge at LTF 4 min caudal to the obex, and then further descend to DLF before reaching the thoracic IML.

In 25 cats under intraperitoneal alpha-chloralose (40 mg/kg) and urethane (400 mg/kg) anesthesia, cardiovascular reactive sites of locus coeruleus (L.C) were stimulated by rectangular pulses (0.5 ms, 80 Hz, 100 to 200 microA) and/or by microinjection of sodium glutamate (Glu, 0.25 M, 70-150 nl). Changes of systemic arterial blood pressure (SAP) and sympathetic vertebral (VNA) and renal (RNA) nerve activities following stimulations were analyzed and, furthermore, SAP responses were compared before and after precollicular decerebration (PD). Microinjection of Glu in this region often produced a moderate increase and less often decrease in SAP. Depressor points were located dorsal to the sites eliciting pressor responses. In the majority of LC stimulations (69%) VNA increased along with the increase of SAP, while the RNA decreased. In a few stimulations marked increase in VNA and decrease in RNA occurred with little change in SAP. PD itself produced various degrees of a temporary (lasted for 5 to 15 min) decrease in SAP from 40 to 100 mmHg. Following PD, three types of change in the LC induced SAP responses were observed in a decreasing order, i.e., the responses were slightly reduced or slightly augmented, or the LC induced depressor responses were converted to a pressor one. Findings of the present study showed that neural mechanism in LC responsible for the changes of SAP and sympathetic nerve activities may exist in a topographic organization. LC is different from the gigantocellular tegmental field (FTG) located in the same rostral pons. The marked pressor responses elicited by activation of the FTG depend entirely on the rostral brain structure, while LC is not. Some brain structures rostral to superior colliculi may exert both inhibitory and excitatory influences over LC in cardiovascular integration.

In cats activation of the dorsal facial area (DFA) in the medulla produced an increase of blood flow in the common carotid artery (CCA). This involves flow increases in both intra-and extra-cranial vessels via cranial parasympathetic nerves. In this study, we attempted to explore transmitter mechanisms involved in vasodilatation in extracranial vascular beds due to DFA activation. Cats were anesthetized with intraperitoneal urethane (350 mg/kg) and chloralose (35 mg/kg). Electrical stimulation (100 μA, 20 Hz, 0.5 ms for 5 s) or microinjection of sodium glutamate (Glu, 0.25 M, 50 nl) in DFA increased the velocity of flow in CCA ipsilateral to the stimulation. After control values were obtained, the animals were subjected to decerebration with transection level just rostral to superior colliculi (precollicular decerebration). The increased CCA flow velocity induced by DFA activation was not altered before and after decerebration. Atropine (muscarinic blocker, 0.5–2.0 mg/kg, i.v.) alone only partially attenuated the increase, but the increase was totally blocked by additional Nω- l -arginine methyl ester (nitric oxide synthase inhibitor) in 7 out of 9 cats. These findings suggest that extracranial vasodilatation induced by DFA activation does not depend on the sympathetic nervous system, but involves the muscarinic- and nitric-oxide-mediated systems.

Thirty-three cats under intraperitoneal chloralose (40 mg/kg) and urethane (400 mg/kg) anesthesia were used to explore the effect of microinjections (100 nl) of carbachol (CCh, 0.5 M), a cholinergic analogue, glycine (Gly, 1 M) and gamma aminobutyric acid (GABA, 0.4 M) on the cardiovascular-reactive sites in the pontomedulla that responded to microinjection of monosodium glutamate (Glu, 0.25 M, 100 nl) resulting in changes of systemic arterial pressure (SAP). Brain sites under exploration included gigantocellular tegmental field and lateral tegmental field (FTG-FTL), the dorsomedial (DM) and ventrolateral (VLM) medulla which produced pressor responses; caudal VLM (CVLM) and paramedian reticular nucleus (PRN) which produced depressor responses. It was found that CCh produced significant fall of SAP in DM and VLM while the rise of SAP in the same site by Glu. CCh produced SAP decrease in CVLM similar to Glu. GABA significantly caused a slight to moderate increase of SAP in FTG-FTL, DM and VLM, and decrease of SAP in CVLM, all in direction similar to that of Glu. Gly produced significant and marked increase of SAP in DM and VLM similar to Glu both in magnitude and duration. Gly produced increase of SAP in CVLM but the fall of SAP by Glu. PRN was relatively non-reactive except a few microinjections of CCh which produced hypotension. In conclusion, the cardiovascular-reactive sites in the pontomedulla that respond to Glu may also react to other chemicals or neurotransmitters. It is highly possible that multiple receptors of different nature co-exist in neurons of some cardiovascular regions in the pontomedulla.

Evoked potential methods were used to compare the patterns of responses to periaqueductal grey (PAG) stimulation in two major medullary sympathoexcitatory areas, namely, ventrolateral medulla (VLM) and dorsal medulla (DM). Adult cats were anesthestized with chloralose and urethane, paralyzed, ventilated and bilaterally vagotomized. Pressor points in the PAG were identified with rectangular pulses in 80 Hz, 200 microA, 0.1 ms and used as stimulation points. Pressor points in VLM and DM were identified by injection of 100 nl of 0.25 M glutamate solution. Adjacent points 1 mm away from these pressor points where injected the same amount of glutamate solution elicited very little blood pressure changes were used as control recording points. Stimulation of the PAG pressor points with rectangular pulse in 1 Hz, 0.1 ms, 200 microA elicited complex evoked field potentials in both VLM and DM. In 9 of the 13 pressor-control pairs tested, distinctive evoked potential of long latency were seen in the pressor point only. These evoked potentials, averaged 3.5 ms in the DM, and 5.6 ms in the VLM. Therefore, it was postulated that pressor points of PAG had separate and independent connections with DM and VLM.

In 26 cats anesthetized with alpha-chloralose and urethane, cardiovascular changes during asphyxia in hypoglycemia and hyperglycemia were studied. Systemic hypoglycemia (serum glucose decrease from 148 to 31 mg/100 ml) was produced by i.v. injection of insulin 20 U/kg, followed by continuous I.V. infusion of 10 U/kg/hr. Systemic hyperglycemia (serum glucose increase from 187 to 657 mg/100 ml) was produced by I.V. infusion of 25% glucose at a rate of 1.5 gm/kg/hr. During hypo- or hyperglycemia, resting mean systemic arterial pressure (MSAP) and heart rate did not change significantly. Brain transection at various levels, i.e., midcollicular decerebration, ponto-medullary or medulla-spinal transection progressively decreased the resting MSAP, but not the heart rate. The most apparent reduction was at the medulla-spinal junction. After induction of systemic hypo- or hyperglycemia, plasma catecholamine concentrations increased significantly. Further increase occurred during asphyxia. Increases of MSAP and plasma catecholamine concentrations during asphyxia were attenuated after midcollicular decerebration and decreased further after subsequent ponto-medullary and medulla-spinal transections. Increases in plasma catecholamines during asphyxia were greater in hypoglycemic than those in hyperglycemic state. The increase in plasma catecholamine persisted in hypoglycemic animals during asphyxia after midcollicular decerebration and ponto-medullary transections. As the terminal stage of asphyxia approached spasmodic contractions of urinary bladder occurred. Bladder contractions were abolished after intracerebroventricular (lateral) injection of insulin (0.25 unit/kg). In conclusion, asphyxia produced very marked cardiovascular and plasma catecholamine responses during hypo- or hyperglycemia and more so during the former condition. These reactions depend mainly on the neural mechanisms of medullary structures. Neural structures rostral to the midcollicular level are not essential.

In 30 cats under chloralose (40 mg/kg) and urethane (400 mg/kg) anesthesia, the ponto-medullary region involved in cardiovascular integration were stimulated by rectangular pulses (0.5 ms, 80 or 5 Hz, 100 to 200 microA) and/or by microinjection of sodium glutamate (Glu, 0.25-0.5 M, 70-200 nl). Changes of systemic arterial blood pressure (SAP) and renal sympathetic nerve activity (RNA) following stimulation were compared before and after precollicular decerebration. Precollicular decerebration itself resulted in an immediate but brief (5 to 15 min) hypotension with a decrease in SAP ranging from 40 to 100 mmHg. Stimulation of the lateral tegmental field (FTL) produced depressor responses. After precollicular decerebration, the stimulation induced depressor responses were either abolished or converted to mild pressor responses. Stimulation of the dorsal gigantocellular tegmental field-periventricular grey (dFTG-PVG) produced pressor responses. These responses were abolished after precollicular decerebration without exception. On the other hand, precollicular decerebration did not reduce pressor responses produced by stimulation of the ventrolateral medulla (VLM) and the dorsal medulla (DM). In 7 additional cats killed with an overdose of pentobarbital, the brain stem were processed for dopamine beta-hydroxylase (DBH). The pressor areas of the VLM and DM were DBH positive, indicating the presence of norepinephrine, while the dFTG-PVG and FTL were not. These findings suggest that the depressor mechanism of the FTL and the pressor mechanism of the dFTG, but not of the VLM or DM depend on actions of the brain structures rostral to superior colliculi.

1. In chloralose-urethane anaesthetized cats, the dorsal cardiovascular reactive area (DCRA) in the parvocellular reticular nucleus dorsomedial to the facial nucleus, and the ventral cardiovascular reactive area (VCRA) ventromedial to the facial nucleus, were stimulated by microinjections of sodium glutamate (100-200 nmol) or electric current. 2. Stimulation of DCRA, with a long latency of 15-20 s, elicited a marked increase of blood flow in the contralateral femoral artery with little change to moderate increase in systemic arterial blood pressure (ABP). In the relatively dorsal portion of DCRA, however, a smaller increase of blood flow in the ipsilateral femoral artery was elicited. 3. On the other hand, stimulation of VCRA with a short latency (3-5s) evoked an increase of blood flow in both femoral arteries which was more prominent on the contralateral side. The responses were accompanied with decreases in the blood flow of other vascular beds with only a slight increase or minimal change in ABP. 4. The data suggest that DCRA and VCRA are both viscerotopically organized to alter the resistance of individual vascular beds for redistribution of blood flow.

In 14 cats anesthetized with chloralose (40 mg/kg) and urethane (400 mg/kg) the pressor area in the ventrolateral periaqueductal grey (PAG) of midbrain was activated by rectangular pulses. The induced increases of systemic arterial pressure (SAP) and plasma norepinephrine (NE) and epinephrine (EPi) were compared before and after destructing portion of cell bodies (sparing passing fibers) in the pressor sites of dorsal (DM) and rostral ventrolateral medulla (VLM) by microinjection of kainic acid. Destruction on VLM or DM reduced the PAG-induced pressor responses and increases in plasma NE and EPi. The reduction of pressor responses, however, was more predominant following VLM than DM destruction. On the other hand, the decrease in plasma NE, was slightly more apparent following DM than VLM destruction.

The importance of the sympathetic nervous system in the genesis of ventricular arrhythmias associated with acute myocardial ischemia (AMI) was assessed in urethane-chloralose anesthetized cats. AMI was created by a ligation of the left anterior descending coronary artery. All control cats developed ventricular tachyarrhythmia (VT), ventricular fibrillation (VF), bradycardia and hypotension, resulting in 50% mortality. In other groups the paramedian reticular nucleus (PRN) was intermittently stimulated to inhibit the sympathetic nervous system. Both sides of the stellate ganglia (SG) or adrenal glands (AG) were removed to exclude direct effects of cardiac sympathetic nerve or indirect effects of circulatory catecholamines from the adrenal medulla on the heart, respectively. AMI did not affect plasma norepinephrine (NE) and epinephrine (EPI) concentrations in all groups. However, NE concentration was higher in SG removed but lower in AG removed group. Removal of SG and stimulation of PRN significantly reduced arrhythmia score and the incidence of VT, VF and mortality. Removal of AG appeared to be less effective. These findings suggest that cardiac sympathetic innervation is more important than neural and adrenal catecholamine secretions in the plasma.

Changes of the nerve activity of the sympathetic renal and vertebral nerves were elicited by microinjection of sodium glutamate (50 nmol/100 nl) into the pressor areas of the dorsal (DM) and rostral ventrolateral medulla (RVLM) in cats under urethane-chloralose anesthesia. Animals were bilaterally vagotomized, artificially ventilated, and paralyzed with gallamine triethiodide. The vertebral nerve activity always increased when pressor responses were induced by DM or RVLM stimulation. However, the effects of medullary stimulation on the renal nerve activity were variable. Three types of renal nerve responses concomitant with the pressor responses were observed in either baroreceptor-intact or baroreceptor-denervated cats. They were: (1) augmentation (type I); (2) attenuation (type II); and (3) insignificant change (type III). Type I responses were often elicited by RVLM stimulation whereas type II responses were often elicited by DM stimulation. Findings suggested that neurons integrating these sympathetic nerve activities were not equally distributed in the pressor areas of DM and RVLM. This result supports the notion that neurons located in different pressor areas of the brainstem exert differential effects over different sympathetic nerve activities.

The effects of electrical stimulation and microinjection of sodium glutamate (0.5 M) in the sympathetic pressor areas of the dorsal medulla (DM), ventrolateral medulla (VLM), and parvocellular nucleus (PVC) on the knee jerk, crossed extension, and evoked potential of the L5 ventral root produced by intermittent electrical stimulation were studied in 98 adult cats anesthetized with chloralose and urethane. During electrical and glutamate stimulation of these pressor areas, in addition to the rise of systemic arterial blood pressure marked inhibition of the spinal reflex was produced, indicating presence of neuronal perikarya responsible for these actions. Mild to moderate augmentation of spinal reflexes was also observed during brain stimulation but only in a few cases. The magnitude of the somatic effects among the pressor areas of the VLM, DM, and PVC subsequent to glutamate activation was about the same. Induced spinal reflex inhibition, independent from the baroreceptor and vagal influence, remained essentially unaltered after acute midcollicular decerebration. The inhibition was also observed in cats decerebellated 8-10 days in advance. The inhibition was not affected after bilateral electrolytic- or kainic-acid-induced lesions in the paramedian reticular nucleus (PRN). On the contrary, PRN-induced spinal reflex inhibition was attenuated after bilateral lesions in the DM or VLM. Data suggest that there coexists neuronal subpopulations in the VLM, DM, and PVC that can affect both the sympathetic pressor systems and spinal reflexes.

To examine whether neuronal cell bodies (perikarya) in the pressor areas of dorsal medulla or ventrolateral medulla also modulate respiratory function, phrenic nerve activity was monitored and correlated with the pressor response in chloralose-urethane anaesthetized cats. The animals were paralyzed and artificially ventilated maintaining the end-tidal fractional concentration of CO2 at 0.04-0.05. The same pressor point in the dorsal or ventrolateral medulla was stimulated electrically (rectangular pulse of 20-200 microA, 80 Hz and 0.5 ms) and then chemically (0.25-0.5 M sodium glutamate, 80-200 nl). Areas producing pressor effects in either the dorsal or ventrolateral medulla produced a current-dependent decrease of phrenic discharge. The decrease in Pna was significant when the electrical current reached 50 microA or above. It occurred immediately before the onset of increase in blood pressure. Injection of glutamate to the same pressor point in either the dorsal or ventrolateral medulla produced a similar decrease in phrenic nerve activity. The results suggest that in the pressor areas of dorsal and ventrolateral medulla there are neuronal perikarya that can increase systemic arterial pressure and inhibit phrenic nerve activity. Whether the same or separate neurones are responsible for these responses is to be determined.

Cardiorespiratory responses, including changes of systemic arterial pressure (SAP), renal or splanchnic sympathetic nerve activity (SNA) and phrenic nerve activity (PNA), were elicited by microinjection of monosodium glutamate solution (0.5 M, 100 nl) into the dorsal (DM) and rostral ventrolateral medulla (RVLM) in 15 vagotomized cats anesthetized by urethane-chloralose and paralyzed by gallamine triethiodide. Artificial ventilation was adjusted to keep the end-tidal CO2 concentration at 4.0-0.5%. Sixty two pressor and 17 non-pressor sites were stimulated. Most of the stimulations inhibited the PNA. The responses of SNA was variable, showing increases, decreases or no change. Inhibition of SNA during SAP increase was not secondary to baroreceptor activation as the inhibition persisted in carotid sinus/aortic denervated animals. Although various combinations of changes of SNA and PNA were observed, their temporal courses were similar in many instances. Attenuation of SNA and PNA was synchronized, suggesting that these changes are coupled in the stimulating sites. The findings suggest that some neurons in DM and RVLM act as a functional unit to modulate cardiorespiratory functions whereas others simply coexist in the same area independent from each other.

The cardioinhibitory mechanisms (bradycardia) of the gigantocellular reticular nucleus (GRN) of medulla was studied in chloralose-urethane anesthetized cats by means of microinjection of sodium glutamate (0.5 M, 100 nl) and single neuron recording. Microinjection of glutamate excited the GRN neurons and produced the bradycardiac responses. The rostral GRN (rostral to the caudal superior olivary nucleus) had higher proportion of bradycardiac loci than the caudal GRN. This suggests that the density of cardioinhibitory neurons in GRN is higher in the rostral than the caudal level. Seventy-eight GRN neurons were recorded extracellularly. Activities of 60 neurons were tested if they were correlated with cardiac rhythm or systemic arterial blood pressure (SAP) changes following intravenous norepinephrine or nitroglycerin. Among these neurons 45% (27/60) exhibited changes related to SAP and 25% (15/60) related to cardiac rhythm. Sixty-one GRN neurons were tested by antidromic activation to determine whether they have axonal projection to the dorsal motor nucleus of vagus and nucleus tractus solitarius (DMN/NTS). Eighteen percent (11/61) of them had axonal projections to the DMN/NTS. These findings suggest that: (i) In GRN there are neurons which mediate cardioinhibition. (ii) These neurons may receive baroreceptor inputs. (iii) They may decrease heart rate through the DMN/NTX.

The afferent and efferent connections between the cardioinhibitory area in the midbrain tegmental field (CIM) and brain stem structures related to cardiovascular integration in cats were investigated by horseradish peroxidase (HRP) for both cell origins and axonal terminations and by chemical (kainic acid) lesion for topographic pathways. Retrogradely labeled neurons were observed in the gigantocellular reticular nucleus (GRN), the pontine reticular nucleus of the pons (PON), the ambiguus nucleus (AN) and the paramedian reticular nucleus (PRN). A few neurons were also labeled in the following structures i.e., ventrolateral medulla (VLM), dorsomedial medulla (DMM), dorsomotor nucleus of the vagus nerve (DMV) and nucleus of solitary tract (NTS). Anterograde HRP labeled terminals were found surrounding the cell bodies of the aforementioned structures. They were most abundant in VLM, DMM, DMV, NTS, moderate in GRN, PRN and AN, but only scanty in hypothalamus. The fiber pathway of CIM neurons was also traced by degenerating fibers consequent to kainic acid lesion and by means of silver stain. Degenerating fiber bundle was found primarily projecting through the medial portion of the mesencephalic pontine structures. As the bundle reached the medulla oblongata, it bifurcated into a dorsal and a ventral tracts on its course. The dorsal tract was primarily coursing through the dorsomedial area, including DMM, NTS and DMV, and the ventral tract was mainly passing VLM, AN and inferior olivary nucleus (ION) areas. The present findings suggest that neurons in the CIM may receive inputs from various cardiovascular-related structures and make output bilaterally to some of pontine and medullary structures to modulate cardiovascular functions. Based on the anatomical findings, the profound bradycardia produced by CIM stimulation may be mediated through the following mechanisms: A. Direct activation of vagal preganglionic neurons in DMV, AN and ION. B. Indirect activation of neurons in GRN for vagal activation and of neurons in PRN for sympathetic inhibition.

Phrenic and renal nerves activities, spinal reflex (knee jerk and the evoked monosynaptic reflex response from the 5th lumbar ventral root), motility of the stomach, duodenum, jejunum and colon, and motility of urinary bladder during and after the lethal asphyxia were studied in cats under intraperitoneal urethane (400 mg/kg) and chloralose (40 mg/kg) anesthesia. Asphyxial anoxia produced one or two peaks of elevation of systemic arterial pressure (SAP) followed by a progressive decrease of SAP and narrowing of pulse pressure and eventual complete cardiovascular arrest. The phrenic nerve activity increased markedly during the final asphyxial SAP elevation; it then decreased along with the decline of SAP and ceased permanently when the SAP reached about 50 mmHg. The renal nerve activity increased along with each phase of pressure elevation. During the terminal stage of progressive SAP fall, the renal nerve activity fluctuated up and down 2-3 times before the SAP dropped to zero, and the activity persisted for an average of 202 sec thereafter. Data suggest that the motoneurons of the phrenic nerve in the cervical spinal cord and medulla oblongata are more vulnerable to asphyxia than the motoneurons responsible for the spinal reflex in the pathway from medulla, the intermediolateral column of the spinal cord and the celiac ganglion. During anoxia, the lumbar spinal reflex showed an initial inhibition then potentiation afterward. Even after the SAP had reached zero, the spinal reflex could still be elicited for one to a few minutes. This suggests that the spinal cord can function sometime after complete cardiac arrest subsequent to asphyxia. The motility of the stomach, duodenum, jejunum, colon and urinary bladder usually decreased during the period of pressure elevation. However, the activity was enhanced during the terminal stage of pressure decline. The enhancement of the colon and bladder motility, spasmodic in nature, was particularly prominent, more so than the others. After complete cardiovascular arrest, the motility of the above viscera became temporary quiescent but about 10 minutes later, it resumed activity again with an enhancement of action in some of the animals. The motility, persisted from few minutes to over six hours. These phenomena indicate that despite a complete deprivation of circulatory and respiratory supports, or death of the animal, the viscera can still contract for a certain period of time.

In chloralose-urethane-anesthetized cats, electrical stimulation and glutamate injection on a small reticular area just dorsal to the facial nucleus (DFA) elicited an ipsilateral reduction in the common carotid resistance (CCR-reduction) with no or minimal change in other cardiovascular parameters. CCR-reduction was mediated via facial and glossopharyngeal nerves, involving partially muscarinic and partially non-muscarinic mechanisms.

Bradycardia was produced by electrical stimulation and injection of glutamate (200 nl, 1 M) to the regions in and around the extremely caudal parts of the inferior olivary nucleus (ION) in chloralose-urethane anesthetized cats. Either medullary transection at 4 mm rostral to the obex, spinal transection at C2–3 or both transections together did not abolish the ION-induced bradycardia. Bradycardia induced by stimulating one ION was slightly reduced and completely abolished by unilateral and bilateral vagotomies, respectively. The ION-evoked bradycardia was also slightly reduced by a raphe lesion. This lesion together with unilateral vagotomy abolisted only the bradycardia induced from the ION on the vagotomized side. In 28 left vagotomized cats, the left ION-induced bradycardia was subjected to the effects of destroying the right ION, dorsal motor/solitary nucleus (DM/SN) and ambiguus nucleus (AN). The bradycardia was completely abolished by ION lesion (7/7), greatly reduced (7/13) or completely abolished (6/13) by DM/SN lesion, and slightly increased (5/8) or decreased (3/8) by AN lesion. We concluded that cells and/or fibers in and around the ION may project fibers to the ipsilateral DM/SN and through the raphe nucleus to the contralateral ION which may send fibers to the other DM/SN.

In rats, rabbits, and cats anesthetized with alpha-chloralose and urethan, responses of the pressor areas of the dorsal portion (DM) and ventrolateral portion (VLM) of medulla and pons were compared. Electrical stimulation (monopolar square-wave pulses) on monosodium glutamate solution (Glu, 100-200 nl, 1 M) was delivered through an electrode-needle tubing connected to a Hamilton syringe for semimicroinjection. In all three of these species, pressor responses were elicited from both DM and VLM by either Glu or electrical stimulation. The most active parts of DM were found in the dorsomedial reticular formation of the rostral medulla to mid-medulla. In the pons and caudal medulla, the Glu-induced response was mild, although the electrically induced response was marked. Application of kainic acid (KA) to either DM or VLM produced an initial pressor response but was followed by a reduction of the pressure rise on subsequent electrical stimulation. Glu, unlike electrical stimulation, excites neural perikarya, not fibers of passage. KA initially excites the neural perikarya before causing damage that spares axons. These results thus suggest that both DM and VLM contain neural perikarya that mediate pressor effects.

In a previous study (1), one of us demonstrated that warming certain neural elements in the lateral reticular formation of the medulla oblongata of the cat produced tachycardia, slight hypertension, and respiratory inhibition. The present investigation is an attempt to determine whether these neural elements also respond to cooling.Materials and Methods. Twenty cats were anesthetized by intraperitoneal injection of urethane (0.8–1.0 g/kg). Rectal temperature was maintained at about 38° by an electric heater controlled automatically by a Klixon 5CT3 proportional thermoregulator. The trachea was cannulated and both vague nerves were dissected free of surrounding tissue. The right femoral artery was cannulated and the arterial pressure was monitored with a Statham P23AC transducer. Heart rate was monitored with a Grass 5P4 tachograph unit which was triggered by the arterial pulses. Respiratory movements were monitored with a chest pneumograph, connected to a Statham P23BC transducer. All recordings were made...

A cardioinhibitory area in the central tegmental field of the midbrain (CIM) was studied in cats under chloralose-urethane anesthesia. Electrical and chemical (glutamate and DL-homocysteic acid) stimulations in this area produced marked bradycardia accompanied by mostly hypotension or minimal change in arterial pressure and by occasional hypertension particularly in the dorsal portion. CIM excitation potentiated the reflex bradycardia induced by IV phenylephrine, while bilateral electrolytic lesion of CIM neither changed the resting cardiovascular parameters nor the reflex bradycardia. The CIM bradycardia was not affected by supracollicular decerebration, but substantially reduced by unilateral vagotomy and completely eliminated by bilateral vagotomy. Destruction of the ambiguus nucleus (NA) and solitary and dorsal motor nuclei (NTS/DMV) abolished the bradycardia. Midline bisection at the midbrain-pontine level only slightly reduced the bradycardia while at the medullary level it was moderately attenuated. Electrolytic lesion of the cardioinhibitory area in gigantocellular reticular nucleus (GRN) abolished the bradycardia. These findings suggest that CIM is an independent mechanism which may send axons to GRN from which the axons may in turn synapse with the NTS/DMV complex and NA. Its final output may utilize both vagus nerves to modulate baroreceptor reflex in promoting bradycardia.

In chloralose-urethane anesthetized cats, bilateral destruction of the caudal part of the inferior olivary nucleus (ION) produced neither apparent alteration of the basal arterial blood pressure and heart rate, nor discernible influence on the degree of the induced reflex bradycardia by phenylephrine and reflex tachycardia by nitroglycerin. Apart from directly producing cardioinhibition, stimulation of the ION was capable of interacting synergistically with the reflex bradycardia and antagonistically with the reflex tachycardia. Stimulation of the ION was also capable of potentiating the bradycardias induced from stimulating other cardioinhibitory areas, including the ION of the other side and the gigantocellular reticular nuclei of both sides of the medulla. These interactions were still feasible when one vagus nerve remained intact, but not after both nerves were cut. The results suggest that the ION may not be a primary component of the neural loops subserving the baroreceptor reflex arch, but instead, assumes modulatory actions to this reflex mechanism via both vagus nerves.

The effects of diphenylhydantoin (DPH) on cardiac arrhythmias induced by occlusion of the common carotid arteries were studied in vagotomized cats under light chloralose anesthesia. It was found that the mean effective dose of DPH via the i.v. route was 11.0 mg/kg. When DPH was injected into the vertebral artery, the carotid artery or the 4th cerebral ventricle, the mean effective dose was 0.8, 1.2 and 0.32 mg/kg, respectively, When DPH was injected directly into the posterior hypothalamic regions, the mean effective dose was even smaller, i.e., 0.14 mg/kg. On the other hand, when DPH was injected into the left ventricle of the heart, the mean effective dose was 1.7 mg/kg and the dose was significantly increased to 4.4 mg/kg when cerebral circulation was temporarily occluded. The data suggest that DPH exerts a potent antiarrhythmic effect through its action on the central nervous system. For the cardiac arrhythmias induced by occlusion of the common carotid arteries, it appears likely that DPH acts on the posterior hypothalamus.

Chinese J. Physiol 31(2): 79-93, 1988. In cats, the resting systemic arterial blood pressure (SAP) which rises on electrical stimulation of the dorsal medulla (DM), ventrolateral medulla (VLM) and paramedian reticular nucleus (PRN) under anesthesia with 2% halothane in oxygen were compared with those 30 min after termination of the inhalation (with application of lidocaine on the surgical wound and i.v. gallamine 2 mg/kg). The resting SAP under halothane were significantly lowered and functions of the DM and VLM much depressed. The depressor response of PRN stimulation was converted to the pressor one after deprivation of halothane anesthesia. In animals under little anesthetic influence, midcollicular decerebration significantly lowered the resting SAP, but both DM and VLM pressor responses were not significantly changed. In addition, the decerebration significantly diminished the peak pressor effects on PRN stimulation. Findings suggest that rostral neuro-structures do exert tonic influence (both excitatory and inhibitory) on medulla vasomotor functions. This is quite different from the classical concept, first proposed by Dittmar and Owsjannikown (1870s) and still considered nowadays as truthful, that the neural structures rostral to the caudal one third of pons was not critical in maintaining the resting SAP.

Fifty-three vagotomized cats under chloralose were studied for cardiac augmentation, cardioacceleration, and vasomotor reaction on direct stimulation of the medulla oblongata and via reflex activations. Cardiac augmentation as well as other cardiovascular responses could be induced on stimulation of the dorsal medulla or the central cut end of the sciatic nerves, or on occlusion of the carotid arteries. The augmentation and other responses remained essentially unchanged regardless of the presence or absence of the rostral neural structures, including the hypothalamus. The results confirm and support the concept that a central control mechanism for vasomotor reaction and cardioacceleration as well as augmentation resides in the dorsal region of the lower brain stem.

Under chloralose, as well as under pentobarbital anesthesia, stimulation of the dorsal medulla elicited after decerebration a cardioacceleration comparable to that before decerebration. Similar increases in the heart rate were also obtained after additional ablation of the remaining midbrain and portion of the pons. In addition, it is possible in these decerebrate animals to elicit cardioaccelerator reflexes by occluding the common carotid arteries or by stimulating the central end of the sciatic nerve. Our findings are contrary to those reported by Peiss ( J. Physiol., London 151: 225, 1960) and do not support his contention that the dorsal medulla constitutes only an afferent cardioaccelerator pathway to the hypothalamus. Our results support the concept that an important integrative mechanism for cardioacceleration, as well as for vasomotor reaction, resides in the dorsal medulla, and that higher neural structures such as the hypothalamus serve a regulatory function.

The lower brain stem was explored for cardiovascular and respiratory responses by means of local diathermy in 36 urethane-anesthetized and 48 unanesthetized, decerebrate cats. In the lateral reticular formation, extending from the level of the rostral end of the inferior olivary nuclei to the most caudal portion of the medulla oblongata, localized heating decreased both rate and tidal volume of respiration, with marked bradycardia, a slight change in systolic blood pressure, and some increase in pulse pressure. Electrical stimulation of the same area usually induced forceful inspiration associated with no cardiovascular response. The thermally induced bradycardia, but not the decrease of respiration, was abolished by vagotomy or by the administration of atropine. The same diathermy applied locally to the rostral hypothalamus in the same cats evoked mainly acceleration of respiration with little cardiovascular reaction. The present experiments suggest that the lateral reticular formation of the medulla is as sensitive to thermal stimulation as is the rostral hypothalamus. The significance of the medullary thermal sensitivity, however, is not clear.

The lower brain stems of 42 vagotomized, midcollicular decerebrate cats under chloralose anesthesia were explored for vasomotor and cardiac responses by means of the stereotaxic technique. When a stimulus was given through bipolar coaxial electrodes with minute exposures at the tips, it was found possible to localize these responses in very discrete areas in the dorsal reticular formation and the adjacent periventricular gray. With current of slightly higher intensity, comparable responses could also be obtained in the ventrolateral reticular formation. It is suggested that the latter constitutes the hypothalamic efferent pathways, while responses from the dorsal medulla signal the activation of the bulbar pressor and cardioaccelerator mechanism. Further, pressor responses from the medulla on the right side are very often accompanied by marked cardioacceleration and only slight or moderate augmentation of cardiac contractions, whereas those from the left are accompanied by marked augmentation and moderate cardioacceleration. This finding suggests that the medullary sympathetic system descends predominately in the spinal cord of the homolateral side.