Biomedical subjects

D F Cechetto

Publications and source records attributed to D F Cechetto.

At least 37 records · Page 2Linked to original sources

PubMed1995

Time-course of neuropeptide changes in peri-ischemic zone and amygdala following focal ischemia in rats.

Previously, using a middle cerebral artery occlusion model in Wistar rat, we showed autonomic disturbances similar to those seen clinically and observed striking neurochemical changes in cortical and subcortical sites at 5 days following stroke. The neurochemical changes may account for functional recovery and/or autonomic disturbances after focal ischemia. To understand the possible mechanisms and to facilitate future studies, it is necessary to define the time-courses of these changes. Using immunohistochemical staining with the peroxidase-antiperoxidase reaction, the changes in several neuropeptides over the peri-ischemic region and the ipsilateral central and basolateral nucleus of the amygdala were investigated at different times after middle cerebral artery occlusion. In the experimental group, neuropeptide Y immunoreactivity appeared to increase by 6 hours in the peri-ischemic region. Using image analysis to quantify the staining intensity, the change became statistically significant at 1 day, peaked around 3 days, and subsided at 10 days. There was a delayed increase in neuropeptide Y in the ipsilateral basolateral nucleus of the amygdala with a peak around 3 days. Immunoreactive staining for leucine-enkephalin, dynorphin, and neurotensin demonstrated an increase that was localized to the ipsilateral central nucleus of the amygdala with a peak around 3 days and a return to baseline levels by 10 days. The results support a specific time-course for each of the neuropeptides studied and indicate that a survival time of 3 days after focal ischemia is the critical period for examining the relationship between neuropeptide responses and neuronal or functional recovery.

Amygdala↗

PubMed1995

Neurochemical changes following occlusion of the middle cerebral artery in rats.

We have developed a stroke model involving middle cerebral artery occlusion in the rat which elicits changes in cardiac and autonomic variables that are similar to those observed clinically. It is likely that these neurogenic autonomic responses are mediated by changes in neurotransmitter systems subsequent to the stroke. This possibility was investigated by examining changes in immunohistochemical staining for tyrosine hydroxylase, neuropeptide Y, leu-enkephalin, neurotoxins and dynorphin following middle cerebral artery occlusion in the rat. Computerized image analysis was used to provide semi-quantitative measurements of the changes. The ischemic region was centered primarily in the insular cortex. The results indicate that there are significant increases in immunostaining for tyrosine hydroxylase and neuropeptide Y in the insular cortex within the peri-infarct region. Neuropeptide Y staining was also significantly increased in the basolateral nucleus of the amygdala, ipsilateral to the middle cerebral artery occlusion, which did not appear to be included in the infarct. Leu-enkephalin, neurotensin and dynorphin staining was significantly elevated in the central nucleus of the amygdala ipsilateral to the occlusion of the middle cerebral artery. These neurochemical changes are discussed as possible mechanisms mediating the cardiac and autonomic consequences of stroke or as part of a process to provide neuro-protection following focal cerebral ischemia.

Amygdala↗

PubMed1995

Neurotensin in the lateral hypothalamic area: origin and function.

The origin of neurotensin in the lateral hypothalamus was investigated by means of fluorescent retrograde tract tracing and neurotensin-like immunoreactivity. Following fluorescent retrograde tract tracing with FluoroGold combined with neurotensin immunohistochemistry in the rat brain, numerous neurotensin-immunoreactive neurons with projections to the posterior lateral hypothalamic area were identified in the central nucleus of the amygdala, perifornical area and the parabrachial nucleus. Fewer numbers of neurotensin-positive neurons with projections to the lateral hypothalamic area were observed in the bed nucleus of the stria terminalis, lateral septal nucleus, medial preoptic area, peri- and paraventricular nuclei of the hypothalamus, anterior lateral hypothalamic area and dorsal raphe nucleus. In addition, the role of neurotensin in the modulation of autonomic regulatory input from the insula was investigated. The lateral hypothalamic area was surveyed for single units responding to electrical stimulation (500-900 microA, 0.5 Hz) of sites in the insular cortex from which cardiovascular pressor or depressor responses could be elicited. These units were tested for the influence of neurotensin on responses to stimulation of the insular cortex. Of 60 spontaneously firing neurons, 27 units responded to electrical stimulation of cardiovascular sites in the insula. Of the units responding to stimulation of cardiovascular sites in the insula, 14 units showed excitation only, 10 units showed excitation followed by inhibition and three units showed inhibition. Iontophoresis of 0.1-1.0 mM neurotensin (25-100 nA, pH 5.0-6.0) potentiated six of the excitatory responses and showed no effect on the inhibitory responses. In addition, nine neurons showed an increase in spontaneous activity with iontophoresis of neurotensin. Of these neurons, three were excited by insular stimulation and six did not respond. These findings indicate the likely origin of neurotensin in the lateral hypothalamic area and demonstrate that neurotensin has a role in the modulation of some of the cardiovascular regulatory input from the insular cortex.

Amygdala↗

PubMed1995

Autonomic responses of the insular cortex in hypertensive and normotensive rats.

Lesion and focal cerebral ischemia of the insular cortex (IC) results in elevated renal sympathetic nerve activity (RSNA) and arterial pressure (AP) in the Wistar rat, while the opposite effect is observed in the spontaneously hypertensive rat (SHR). Acute changes in AP, heart rate (HR) and RSNA were measured in propofol-anesthetized and conscious SHR (n = 17) and Wistar rats (n = 17) during pressure injection of D,L-homocysteic acid (DLH; 100 mM) and lidocaine (LID; 20 mg/ml) into the IC. DLH injections (200 nl) into the IC of anesthetized Wistar rats resulted in a significant increase in MAP (mean change = +27 +/- 7 mmHg; P < 0.05) and a significant decrease in HR (-22 +/- 9 beats/min) and RSNA (-11 +/- 4 microV.s). Neither DLH nor LID injections into the IC of anesthetized SHR affected MAP or RNA. DLH and LID injections (500 nl) into the IC of conscious Wistar rats both resulted in a significant increase in MAP (+26 +/- 5 mmHg; 11 +/- 4 mmHg, respectively). Neither DLH nor LID injections had any cardiovascular effects in the conscious SHR. It therefore appears that the IC of conscious Wistar rats has a tonic inhibitory output, while neural excitation is capable of eliciting pressor responses. Conversely, the IC of SHR appears to exert no tonic influence on MAP.

Animals↗

PubMed1995

Neurochemical interactions in the parabrachial nucleus mediating visceral inputs to visceral thalamic neurons.

Previously we demonstrated that glutamatergic and noradrenergic receptors mediate the relay of visceral information through the parabrachial nucleus (PBN) and that calcitonin gene-related peptide (CGRP), substance P (SP), somatostatin (SOM), neurotensin (NT), and cholecystokinin (CCK) may modulate these responses. The interactions of these neurotransmitters and neuropeptides were examined in male Wistar rats (17) that were anesthetized with chloral hydrate and ventilated and in which blood pressure and heart rate were continuously monitored. The left cervical vagus nerve was stimulated at submaximal current intensities to elicit changes in single and multiunit activity of visceral thalamic neurons (VTNs). Peristimulus-time and continuous-time histograms of VTN activity were made before and after 200-nl injections of peptides, neurotransmitter agonists or antagonists, or artificial cerebrospinal fluid into the PBN. Combined injection of CGRP and SP into the PBN produced a synergistic inhibition of spontaneous VTN activity and the vagally evoked VTN response. Combined injection of NT and phenylephrine (PE) into the PBN produced only an additive increase in the spontaneous activity of VTNs. Prior administration of SOM in the PBN blocked the excitatory action of an alpha-adrenergic agonist (phenylephrine) injection on the spontaneous activity of VTNs, whereas CGRP, SP, or CCK had no effect on the alpha-agonist-induced response. Prior injection of an alpha-adrenergic antagonist (phentolamine) prevented the excitatory effect of NT in the PBN. Injection of CGRP, SP, NT, or CCK into the PBN did not change the response of VTNs to application of glutamate. These results suggest mechanisms for peptide interaction with primary neurotransmitters in the PBN and indicate whether the neuropeptides are acting before the primary neurotransmitter synapse or postsynaptically.

Animals↗

PubMed1995

Insular lesion evokes autonomic effects of stroke in normotensive and hypertensive rats.

BACKGROUND AND PURPOSE: Increases in sympathetic activity and frequency of myocardial damage occur after middle cerebral artery occlusion (MCAO) in Wistar rats, while MCAO in the spontaneously hypertensive rat (SHR) decreases sympathoadrenal activity. Autonomic changes have been suggested to result from damage to the insular cortex (IC). METHODS: A lesion of the IC was made using the excitotoxin D,L-homocysteic acid (DLH; 1 mol/L), in urethane-anesthetized Wistar rats and SHRs. Mean arterial pressure (MAP), heart rate, renal sympathetic nerve discharge (SND), ECG, and plasma catecholamines were measured in 14 SHRs and 14 Wistar male rats after a 500-nL injection of DLH or phosphate-buffered saline (PBS) into the IC. RESULTS: Histological examination showed that DLH resulted in neuronal damage throughout the IC. DLH injection initially elevated MAP (at approximately 10 minutes after injection) in Wistar rats but not in SHRs. At 4 hours after the DLH injection, there was a secondary, longer-term increase in MAP in the Wistar rats. MAP decreased in the SHRs after IC lesion such that at 6 hours, lesioned SHRs had a MAP that was significantly lower than that of sham-lesioned SHRs. SND initially increased (at 10 minutes) after DLH injection in Wistar rats. In the SHRs, SND decreased significantly from the initial values, by 3 hours after DLH injection. Plasma catecholamine levels were not significantly changed as a result of IC lesion in the Wistar rats or the SHRs. Heart rates increased in all animals, with no differences between groups. There were no changes in the ECG or in the frequency of cardiac myocytolysis in either strain (sham or lesioned animals). CONCLUSIONS: IC lesion in the SHR and Wistar rat therefore appears to result in autonomic changes similar to that seen after MCAO. Unlike MCAO, however, the autonomic changes do not appear to be sufficient to produce myocardial damage.

Animals↗

PubMed1994

Natriuretic effect of rilmenidine in anesthetized rats.

Rilmenidine binds to alpha 2-adrenoceptors and imidazoline receptors in the central nervous system and the kidney. To test the hypothesis that rilmenidine would increase sodium excretion, renal function was studied in rats with innervated and denervated kidneys to distinguish between indirect (via renal sympathetic nerves) and direct effects of rilmenidine on the kidney. Standard clearance techniques were used in Wistar rats anesthetized with thiobutabarbital to measure renal function during 80 minutes of infusion of 0.9% NaCl or rilmenidine (20 or 50 micrograms.kg-1.min-1 intravenously). Snares on abdominal arteries were used to offset hypotension induced by rilmenidine. Heart rate decreased by 80-120 beats/min with either dose of rilmenidine. At 20 micrograms.kg-1.min-1, rilmenidine increased total and fractional excretion of sodium and clearance of osmoles while decreasing free water clearance from innervated kidneys. There were no changes in these variables in chronically denervated kidneys. Direct recording of renal sympathetic nerve activity showed a progressive, marked decrease in nerve activity during the low-dose infusion of rilmenidine. At 50 micrograms.kg-1.min-1, rilmenidine produced a differential effect on the clearance of osmoles by innervated and denervated kidneys but both kidneys had an increase in free water clearance. The data indicate that rilmenidine increases sodium excretion indirectly in anesthetized rats by decreasing renal sympathetic nerve activity. At doses and infusion periods used in these studies, there was no evidence for a direct effect of rilmenidine on sodium excretion. The increase in free water clearance seen with the high dose of rilmenidine suggests that the inhibitory effect of alpha 2-adrenoceptor activation on vasopressin is involved at this dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic Fibers↗

PubMed1994

Serotoninergic and nonserotoninergic neurons in the medullary raphe system have axon collateral projections to autonomic and somatic cell groups in the medulla and spinal cord.

Fluorescent double retrograde-tracing studies combined with fluorescent immunostaining for serotonin were carried out to determine the potential patterns of divergence in axonal projections to autonomic and somatic motor sites from medullary raphe and parapyramidal neurons. Injections (20-60 nl) of combinations of fluorescent retrograde tracers (Fast Blue, fluoro-gold, green latex microspheres, Diamidino Yellow) were made into the intermediolateral cell column (IML) of the spinal cord and the brainstem lateral tegmental field or ventral horn of the lumbar spinal cord of male Wistar rats. The animals were perfused after a 7-10-day survival period, and the brains were removed, sectioned (50 microns), and immunostained for serotonin. Following injections of different retrograde-tracer substances into the IML of the thoracic cord and the ventral horn of the lumbar cord, 36% of the neurons with axon collateral projections to the IML and the lumbar ventral horn were serotoninergic. Following injections of different retrograde-tracer substances into the IML and the lateral tegmental field, 26% of the neurons with axon collateral projections to the IML and the lateral tegmental field were serotoninergic. Many of the medullary neurons with projections to the lateral tegmental field and the lumbar cord were located dorsal and lateral to those neurons with projections to the IML. The results indicate that serotoninergic and nonserotoninergic neurons of the midline raphe system and parapyramidal region have axon collateral branches to the IML and the lateral tegmental field or the IML and the lumbar ventral horn. These projection neurons may form the anatomical substrate for the integration of autonomic and somatic motor activity.

Amidines↗

PubMed1994

Spinal cord regulation of sympathetic activity in intact and spinal rats.

Excitatory amino acid (EAA) and cholinergic neurotransmission in the spinal cord of urethan-anesthetized rats was investigated to assess mechanisms regulating sympathetic activity after spinal cord injury. Blockade of EAA transmission by intrathecal injection of kynurenic acid decreased arterial blood pressure by 24 +/- 4 mmHg, heart rate by 15 +/- 10 beats/min, and renal sympathetic nerve activity (RSNA) by 85 +/- 4% in intact rats. In rats with cervical spinal transections, this blockade decreased RSNA by 51 +/- 5% and had no effect on arterial pressure and heart rate. Muscarinic blockade by intrathecal atropine decreased RSNA by 12 +/- 3 and 32 +/- 6% in intact and spinal rats, respectively, and caused no cardiovascular responses in either group. Combined blockade of EAA and muscarinic receptors in spinal rats decreased RSNA by 77 +/- 1%. Intrathecal injections of the EAA agonist D,L-homocysteic acid in spinal rats caused initial increases (335 +/- 28%) in RSNA lasting approximately 3 min and later sustained increases (157 +/- 19%) lasting 36 +/- 8 min. Only the early excitation increased arterial pressure by 17 +/- 3 mmHg, and then pressure returned to baseline values. The EAA agonist kainic acid increased RSNA by 402 +/- 90% in spinal rats, an effect lasting 70 +/- 5 min, and increased arterial pressure by only 8 +/- 2 mmHg for 12 +/- 5 min. These findings suggest that tonic activity of spinal neurons with EAA and cholinergic receptors maintains tonic RSNA after spinal cord transection. However, this activity does not play a major role in maintaining arterial pressure, even if it is increased substantially by EAA receptor stimulation.

Animals↗

PubMed1994

Neurotransmitters in the parabrachial nucleus mediating visceral input to the thalamus in rats.

The putative neurotransmitters in ascending visceral pathways were investigated by recording changes in the response of thalamic neuronal activity evoked by vagal stimulation before and after neurotransmitter antagonist injections into the parabrachial nucleus (PB). Male Wistar rats (n = 39) were anesthetized with chloral hydrate and alpha-chloralose, ventilated, and blood pressure and heart rate were continuously monitored. The left cervical vagus nerve was stimulated to elicit changes in single and multiunit activity in the visceral thalamus. Peristimulus-time histograms of thalamic activity were made before and after 200-nl injections of antagonist or control solution into the PB. Synaptic blockade using cobalt (10 mM) injections into the PB inhibited both the thalamic response evoked by vagal stimulation (86-100%) and the spontaneous firing of thalamic neurons (88-92%). Injections of kynurenate (250 mM) or the N-methyl-D-aspartate (NMDA) antagonist, DL-2-amino-5-phosphonopentanoic acid (AP-5; 200 microM), inhibited (87-94% and 92-100%) the thalamic neuronal response evoked by vagal stimulation. The alpha-adrenergic antagonist, phentolamine (0.1 microM), or the specific alpha 2-adrenergic antagonist, yohimbine (0.1 microM), inhibited the spontaneous firing of thalamic units (42-56% and 64-77%) but had no effect on the vagally evoked response. Bicuculline [gamma-aminobutyric acid (GABA) A-subtype antagonist] significantly enhanced spontaneous thalamic neuronal activity (108-125%) without effect on the vagally evoked response. Atropine (0.1 microM) had no significant effect on either the vagally evoked response or the spontaneous firing of thalamic neurons. These results suggest that the relay of visceral afferent sensory information through the PB is mediated by NMDA receptors and that alpha 2 and GABAA receptors contribute to the tonic activity of ventral basal thalamic neurons receiving visceral input.

Amino Acids↗

PubMed1993

Cardiac and sympathetic effects of middle cerebral artery occlusion in the spontaneously hypertensive rat.

Acute increases in sympathetic activity, plasma catecholamine concentrations and myocardial damage, occur following middle cerebral artery occlusion (MCAO) in Wistar rats. Hypertension is a major risk factor for stroke. The autonomic responses to MCAO in the spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were therefore investigated. Arterial pressure (AP), heart rate (HR), renal sympathetic nerve discharge (SND), plasma catecholamines and ECG were measured in 16 SHR and 16 WKY male urethane-anesthetized rats, which were subjected to either MCAO or sham MCAO. Cerebral infarct size did not differ between SHR and WKY rats, as shown by tetrazolium staining. Initial AP was significantly higher in SHR (96 +/- 4 mmHg) than in WKY (70 +/- 1 mmHg; P < 0.05). No significant differences in initial HR or plasma catecholamine levels were observed between SHR and WKY. By 6 hours after MCAO, AP, SND and plasma epinephrine in SHR decreased significantly, while HR showed a significant increase. SND and plasma catecholamines in the WKY showed increases that did not reach significant levels following MCAO. The QT interval of the ECG was significantly prolonged in the WKY MCAO rats, which also had a higher frequency of cardiac myocytolysis than the other groups. Unlike the increases in autonomic variables following MCAO in Wistar rats, SHR exhibit significant decreases in SND and AP, while WKY show slight, but non-significant increases. These differences in the autonomic reaction to MCAO may reflect genetic differences in the response to cerebral ischemia.

Animals↗

PubMed1993

Functional and anatomical organization of cardiovascular pressor and depressor sites in the lateral hypothalamic area. II. Ascending projections.

Microinjections of L-glutamate or D,L-homocysteic acid were used to stimulate cell bodies in the region of the lateral hypothalamic area (LHA) selectively. Subsequent iontophoretic injections of Phaseolus vulgaris-leucoagglutinin or pressure injections of wheat germ agglutinin-horseradish peroxidase were made into regions containing identified pressor and depressor sites and their connections with the forebrain and cerebral cortex were traced. The results indicate that decreases in blood pressure (10-45 mm Hg) and heart rate (20-70 bpm) could be elicited from tuberal (LHAt) and posterior (LHAp) sites in the LHA and that these regions have ascending projections to the insular cortex, the ventral forebrain including the septal-diagonal band of Broca complex, the ventral palladium, substantia innominata, amygdala, and the lateral preoptic area. In contrast, increases in blood pressure (10-40 mm Hg) and heart rate (20-70 bpm) were elicited primarily from neurons located adjacent to the fornix in the perifornical area (PFA). Injections of tract tracers into this region produced terminal labeling that differed markedly from the pattern seen following injections of tracer into depressor sites in the LHA. In addition, the pattern of anterograde labeling seen following injections of tracer into the anterior PFA differed from that seen following injections of tracer into the posterior PFA. Injections of tracer into the anterior PFA resulted in dense terminal labeling in the medial preoptic area and the parvicellular paraventricular nucleus of the hypothalamus whereas injections into the posterior PFA resulted in dense terminal labeling in the lateral septal nucleus, nucleus accumbens, bed nucleus of the stria terminalis, as well as the medial preoptic area and the parvocellular paraventricular nucleus of the hypothalamus. The results demonstrate that the posterolateral hypothalamus of the rat contains two regions with specific cardiovascular function and highly organized connections with diencephalic, forebrain, and cortical structures.

Afferent Pathways↗

PubMed1993

Peptides in the parabrachial nucleus modulate visceral input to the thalamus.

The role of neuropeptides in ascending visceral pathways was investigated by recording the changes in the response of thalamic neuronal activity evoked by vagal stimulation before and after peptide injection in the parabrachial nucleus (PB). Male Wistar rats (n = 25) were anesthetized with chloral hydrate and ventilated, and blood pressure and heart rate were continuously monitored. The left cervical vagus nerve was stimulated at submaximal current intensities to elicit changes in single and multiunit activity in the parvocellular visceral relay nuclei in the ventral basal thalamus. Peristimulustime histograms of thalamic activity were made before and after 200-nl injections of peptides or artificial cerebrospinal fluid (CSF) controls in the PB. Injection of calcitonin gene-related peptide (CGRP) at 5 mM or substance P (SP) at 2 mM into the PB significantly attenuated the evoked response of thalamic neuronal activity by 87-100% and 85-100%, respectively. Injections of somatostatin (SOM; 1 mM) did not significantly alter the response evoked by vagal stimulation but significantly inhibited the spontaneous firing of thalamic units, resulting in a 10-fold increase in the response-to-background ratio. This suggests that SOM in the PB inhibits cells in a parallel pathway that terminates on thalamic visceral neurons but that are not part of the ascending visceral sensory pathway. Spontaneous thalamic neuronal activity and vagally evoked responses were significantly enhanced (278-508%) by injection of 1 mM neurotensin (NT) in the PB. Cholecystokinin (CCK) at low doses (0.0002-0.2 mM) attenuated while the highest dose, 2 mM, briefly excited the spontaneous activity of thalamic units before inhibiting their activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Experimental cerebral ischemic lesions and autonomic and cardiac effects in cats and rats.

Clinically, a pattern of autonomic and cardiac changes after hemispheric stroke has been observed that includes increased plasma catecholamines, electrocardiographic abnormalities, serum levels of cardiac enzymes, and myocytolysis on autopsy. Experimental models in both the cat and rat have been developed to examine some of the mechanisms responsible for these changes. Middle cerebral artery occlusion (MCAO) in the rat mimicked the increase in plasma catecholamines, electrocardiographic changes, sympathetic nerve discharge, and myocytolysis seen in the patient population. This model was also used to determine that stroke attenuates sympathoexcitatory reflexes and that right-sided strokes and increasing age exaggerate the autonomic and cardiac disturbances. Hypertension does not appear to exacerbate the stroke-induced sympathoadrenal increases. Lesion of the insular cortex mimics the autonomic changes in MCAO animals. Finally, changes in the content of neurochemicals in the insular cortex and amygdala have been measured that may be involved in mediating the autonomic changes elicited by MCAO.

Aging↗

PubMed1993

Renal effects of rilmenidine in anesthetized rats: importance of renal nerves.

Renal function studies using standard clearance techniques were done in control and rilmenidine-infused (20 micrograms/Kg/min i.v. for 80 min) Wistar rats anesthetized with Inactin. The role of renal sympathetic nerves in the action of rilmenidine was assessed using rats in which the left kidney was denervated 7 to 10 days before the experiment. In other experiments, renal sympathetic nerve activity was recorded during infusion of rilmenidine. Arterial pressure and heart rate were decreased significantly by rilmenidine but changes in arterial pressure were limited to 10 to 12 mm Hg by ligating the proximal aorta during infusion of rilmenidine. Under these conditions, rilmenidine did not alter glomerular filtration rate significantly, but renal blood flow increased significantly in both innervated and denervated kidneys. Urine flow, total and fractional sodium excretion, and clearance of osmoles increased significantly in innervated kidneys but not in denervated kidneys. Free water clearance was decreased significantly, but only in the innervated kidney. Potassium excretion and fractional potassium excretion were increased significantly in both kidneys, although the change was larger in the innervated kidneys. Rilmenidine decreased renal sympathetic nerve activity progressively until by 80 min nerve activity was essentially absent. The data indicate that rilmenidine increases renal blood flow and potassium excretion by a mechanism independent of renal nerves, whereas the natriuresis and diuresis is dependent upon intact renal nerves. The increase in fractional excretion of sodium was associated with a marked decrease in renal sympathetic nerve activity suggesting that the natriuresis is caused by decreased tubular reabsorption of sodium subsequent to a central action of rilmenidine.

Adrenergic alpha-Agonists↗

PubMed1992

Lateral hypothalamic area neurotransmission and neuromodulation of the specific cardiac effects of insular cortex stimulation.

Microstimulation of the rat posterior insular cortex in phase with the ECG R wave elicits pure cardiac effects unaccompanied by changes in blood pressure or respiration. This technique has successfully demonstrated cardiac chronotropic organisation and arrhythmogenesis within the insula. Pathways exist linking the insular cortex with the lateral hypothalamic area (LHA). Similarly, the LHA has previously been shown to mediate the sympathetic and blood pressure effects of insular cortex stimulation. Therefore it was anticipated that the tachycardia elicited by insular phasic microstimulation would be responsive to LHA manipulations. Insular tachycardia sites in 28 chloralose-anesthetised male Wistar rats were phasically stimulated once with each cardiac cycle using 500 microA for 1 min before and after microinfusions (390 nl) into the LHA. The insular tachycardia response was abolished by LHA microinfusions of the synaptic blocker cobaltous chloride (4 mM). LHA microinjection of kynurenic acid (250 mM) attenuated insular tachycardia by 95%. Microinjection of naloxone (30 mM) similarly attenuated the tachycardia by 95%. Met-enkephalin (3.5 mM) was without effect on this response whereas Leu-enkephalin (3.5 mM) and neuropeptide Y (0.01 mM) (NPY) doubled the magnitude of the tachycardia. Dynorphin (0.12 mM), a specific kappa opioid receptor agonist, augmented the response to stimulation of insular tachycardia sites 8-fold. Consequently, it is suggested that the LHA contains an obligatory synapse mediating insular tachycardia and that glutamate is the likely neurotransmitter at this site. Neuromodulation of insular tachycardia may be effected by opiate kappa and NPY receptors, a finding of considerable clinical relevance.

Animals↗

PubMed1992

Functional and anatomical organization of cardiovascular pressor and depressor sites in the lateral hypothalamic area: I. Descending projections.

The present study describes the anatomical organization of projections from functionally defined cell groups of the lateral hypothalamic area. Cardiovascular pressor and depressor sites were identified following microinjection (5-50 nl) of 0.01-1.0 M L-glutamate or D,L-homocysteate into the anesthetized rat. Subsequent injections of Phaseolus vulgaris-leucoagglutinin (PHA-L) or wheat germ agglutinin-horseradish peroxidase (WGA-HRP) were made into pressor or depressor sites and their connections with the brainstem and spinal cord were traced. Decreases in blood pressure (10-45 mmHg) and heart rate (20-70 bpm) were elicited from tuberal (LHAt) and posterior (LHAp) regions of the lateral hypothalamic area (LHA). Depressor neurons in the LHAt have descending projections to the central gray, dorsal and median raphe nuclei, pedunculopontine tegmental nucleus, pontine reticular formation, medial and lateral parabrachial nuclei, laterodorsal tegmental region, and medullary reticular formation including the region of the lateral tegmental field, nucleus ambigous, and rostrocaudal ventral lateral medulla. In contrast, descending projections from depressor neurons in the LHAp have dense terminal fields in the rostral, middle, and commissural portions of the nucleus of the solitary tract and the lateral tegmental field as well as the ventrolateral central gray, pedunculopontine tegmental nucleus, and medial and lateral parabrachial nuclei. Both the LHAt and LHAp have light projections to the intermediate region of the cervical and thoracic spinal cord. Increases in blood pressure (10-40 mmHg) and heart rate (20-70 bpm) were elicited almost exclusively from neurons located medial to the LHAt and LHAp in a region surrounding the fornix, termed the perifornical area (PFA). Pressor cells in the PFA have descending projections to the central gray, dorsal and median raphe nuclei, laterodorsal tegmental nucleus, and Barrington's nucleus as well as a light projection to the commissural portion of the nucleus of the solitary tract and the intermediate region of the cervical and thoracic spinal cord. The retrograde labeling observed in the WGA-HRP studies indicates that cells in most terminal fields have reciprocal projections to the pressor and depressor regions of the LHA. The results demonstrate that groups of neurons in the lateral hypothalamus with specific cardiovascular function have differential projections to the brain stem.

Amino Acids↗

PubMed1992

Plasma and organ catecholamine levels following stimulation of the rat insular cortex.

The posterior insular cortex of the rat contains an area of cardiac chronotropic representation within which tachycardia sites occur rostrally to those producing bradycardia. In the current study using ketamine-anesthetized rats, the insular cortex was stimulated for 1 h using a phasic technique synchronized with the cardiac cycle. Tachycardia was associated with an increase in plasma norepinephrine concentration; epinephrine remained unchanged. This indicates a neural origin of the norepinephrine increment. The tachycardia response was completely blocked by atenolol. Plasma catecholamine levels remained unchanged during stimulation of insular bradycardia sites. Atenolol was without effect during stimulation-induced bradycardia which was completely blocked by atropine. Total cardiac norepinephrine concentration inversely correlated with change in heart rate during stimulation of tachycardia sites. No correlation between intracardiac catecholamines and heart rate variables was found for the bradycardia or control sites. These results indicate that in the ketamine-anesthetized rat, whereas insular stimulation-induced tachycardia is dependent on the sympathetic nervous system, bradycardia elicited by insular cortex stimulation is mediated by parasympathetic mechanisms. No correlation was identified between renal or skeletal muscle norepinephrine levels and any heart rate parameter. This implies that the sympathetic effects of phasic insular microstimulation may be exerted mainly on cardiac nerves, and less so in other visceral beds.

Animals↗