Effects of hypocretin and norepinephrine interaction in bed nucleus of the stria terminalis on arterial pressure.

Forebrain neuronal circuits containing hypocretin-1 (hcrt-1) and norepinephrine (NE) are important components of central arousal-related processes. Recently, these two systems have been shown to have an overlapping distribution within the bed nucleus of the stria terminalis (BST), a limbic structure activated by stressful challenges, and which functions to adjust arterial pressure (AP) and heart rate (HR) to the stressor. However, whether hcrt-1 and NE interact in BST to alter cardiovascular function is unknown. Experiments were done in urethane-α-chloralose anesthetized, paralyzed, and artificially ventilated male Wistar rats to investigate the effect of hcrt-1 and NE on the cardiovascular responses elicited by l-glutamate (Glu) stimulation of BST neurons. Microinjections of hcrt-1, NE or tyramine into BST attenuated the decrease in AP and HR to Glu stimulation of BST. Additionally, combined injections of hcrt-1 with NE or tyramine did not elicit a greater attenuation than either compound alone. Furthermore, injections into BST of the α2-adrenergic receptor (α2-AR) antagonist yohimbine, but not the α1-AR antagonist 2-{[ß-(4-hydroxyphenyl)ethyl]aminomethyl}-1-tetralone hydrochloride, blocked both the hcrt-1 and NE-induced inhibition of the BST cardiovascular depressors responses. Finally, injections into BST of the GABAA receptor antagonist bicuculline, but not the GABAB receptor antagonist phaclofen, blocked the hcrt-1 and NE attenuation of the BST Glu-induced depressor and bradycardia responses. These data suggest that hcrt-1 effects in BST are mediated by NE neurons, and hcrt-1 likely acts to facilitate the synaptic release of NE. NE neurons, acting through α2-AR may activate Gabaergic neurons in BST, which in turn through the activation of GABAA receptors inhibit a BST sympathoinhibitory pathway. Taken together, these data suggest that hcrt-1 pathways to BST through their interaction with NE and Gabaergic neurons may function in the coordination of cardiovascular responses associated with different behavioral states.

Co-localization of hypocretin-1 and leucine-enkephalin in hypothalamic neurons projecting to the nucleus of the solitary tract and their effect on arterial pressure.

Experiments were done to investigate whether hypothalamic hypocretin-1 (hcrt-1; orexin-A) neurons that sent axonal projections to cardiovascular responsive sites in the nucleus of the solitary tract (NTS) co-expressed leucine-enkephalin (L-Enk), and to determine the effects of co-administration of hcrt-1 and D-Ala2,D-Leu5-Enkephalin (DADL) into NTS on mean arterial pressure (MAP) and heart rate. In the first series, in the Wistar rat the retrograde tract-tracer fluorogold (FG) was microinjected (50nl) into caudal NTS sites at which L-glutamate (0.25 M; 10 nl) elicited decreases in MAP and where fibers hcrt-1 immunoreactive fibers were observed that also contained L-Enk immunoreactivity. Of the number of hypothalamic hcrt-1 immunoreactive neurons identified ipsilateral to the NTS injection site (1207 ± 78), 32.3 ± 2.3% co-expressed L-Enk immunoreactivity and of these, 2.6 ± 1.1% were retrogradely labeled with FG. Hcrt-1/L-Enk neurons projecting to NTS were found mainly within the perifornical region. In the second series, the region of caudal NTS found to contain axons that co-expressed hcrt-1 and L-Enk immunoreactivity was microinjected with a combination of hcrt-1 and DADL in α-chloralose anesthetized Wistar rats. Microinjection of DADL into NTS elicited depressor and bradycardia responses similar to those elicited by microinjection of hcrt-1. An hcrt-1 injection immediately after the DADL injection elicited an almost twofold increase in the magnitude of the depressor and bradycardia responses compared to those elicited by hcrt-1 alone. Prior injections of the non-specific opioid receptor antagonist naloxone or the specific opioid δ-receptor antagonist ICI 154,129 significantly attenuated the cardiovascular responses to the combined hcrt-1-DADL injections. Taken together, these data suggest that activation of hypothalamic-opioidergic neuronal systems contribute to the NTS hcrt-1 induced cardiovascular responses, and that this descending hypothalamo-medullary pathway may represent the anatomical substrate by which hcrt-1/L-Enk neurons function in the coordination of autonomic-cardiovascular responses during different behavioral states.

Evaluation of the Heart and Stroke Foundation of Canada Research Scholarship Program: research productivity and impact.

OBJECTIVE: To compare the research productivity, and its impact, of individuals awarded research scholarships from the Heart and Stroke Foundation of Canada (HSFC) with that of a parallel group of unsuccessful applicants during the funding years 1980/81 to 1989/90 inclusive. Research productivity was defined as the number of peer reviewed publications, and impact was evaluated from the number of publications cited; the number of citations per publication; the number of citations per individual; and the impact score. STUDY SELECTION: Data were collected on 192 individuals. Cohorts were defined as successful and unsuccessful individuals entering the system in the same year. The study comprised 10 separate cohorts. Data were collected on yearly publications and citation counts for each individual. These data, along with journal impact factors, were obtained from the Institute for Scientific Information. CONCLUSIONS: During the 10 years of the study, individuals funded by the HSFC published more papers, more of their papers were cited, and they received more citations per individual than the unfunded comparison group. This consistency in multiple indicators provides strong evidence that funded individuals are more productive and that their work has a greater impact on the body of knowledge in this area. Although this study cannot unequivocally show a direct causal relation between funding and research success, the trend as shown by the indicators studied suggests a beneficial effect.

Effect of preganglionic stimulation or chronic decentralization on neurotensin-like immunoreactivity in sympathetic ganglia of the cat.

In pentobarbital-anesthetized cats, supramaximal stimulation (40 Hz, 2 h) of the preganglionic input to the acutely decentralized right stellate (RSG) or superior cervical (RSCG) ganglion resulted in a decrease in neurotensin (NT)-like immunoreactivity (IR), by 83% in the SG and by 46% in the SCG, as determined by radioimmunoassay. Chronic (7 days) decentralization of the ganglia resulted in a similar depletion of NT-like IR (SG: 86%; SCG: 76%). Supramaximal stimulation (40 Hz, 2 h) of the intact postganglionic outflow of either ganglion had no effect on NT-like IR. These data suggest that NT in the SG and SCG is present in preganglionic axons and is released by activation of these axons.

Organization of ventrolateral medullary afferents to the hypothalamus.

In summary, these anatomical and electrophysiological data have provided evidence to support the suggestion that VLM neurons project directly to regions of the hypothalamus that contain magnocellular neurosecretory neurons. In addition, these results support the suggestion that pathways ascending from the VLM to the hypothalamus function, in part, in the control of the release of the neurohypophyseal hormones by PVH and SON magnocellular neurosecretory neurons during activation of peripheral cardiovascular receptors.

Renal and cardiovascular afferent inputs to hypothalamic paraventriculo-spinal neurons.

Experiments were done in chloralose-anesthetized cats to identify single units in the paraventricular nucleus of the hypothalamus (PVH) that responded to stimulation of afferent renal nerves (ARN) and the buffer nerves (carotid sinus (CSN) and aortic depressor (ADN) nerves), and whose axons projected directly to thoracic spinal sympathetic areas. Of 426 single units tested in the PVH region, 20 were antidromically activated by stimulation of the spinal cord. Sixteen of these antidromic units (80%) responded orthodromically to stimulation of ARN and/or the buffer nerves; 6 units (30%) were excited by ARN stimulation only, 2 units (10%) were excited by both ARN and buffer nerve stimulation, and 6 units were excited and 2 inhibited by buffer nerve stimulation only. These data demonstrate that sensory information originating in renal and cardiovascular receptors alters the firing rate of PVH-spinal projecting neurons and suggest that this long renal-PVH reflex loop may contribute to the elevation of arterial pressure (AP) during conditions when ARN are activated.

Contribution of paraventricular nucleus to afferent renal nerve pressor response.

Experiments were done in alpha-chloralose-anesthetized, paralyzed, and artificially ventilated cats to determine the effect of afferent renal nerve (ARN) stimulation on the firing frequency of neurons in the paraventricular nucleus of the hypothalamus (PVH), whose axons project directly to the neurohypophysis (NH), and the contribution of these neurons to the pressor response elicited by ARN stimulation. In the first series of experiments, 474 single units were extracellularly recorded in the PVH region. Of these units 86 were antidromically excited by stimulation of the NH. Seventeen of the antidromic units (20%) responded orthodromically to ARN stimulation; 10 responded to ARN stimulation only, and 7 units responded to both ARN and buffer nerve stimulation. All PVH-NH-projecting neurons that responded to ARN stimulation were excited. In the second series the contribution of PVH neurons to the pressor response elicited by ARN stimulation was investigated in animals with the aortic depressor, carotid sinus, vagus, and cervical sympathetic nerves cut bilaterally. The ARN pressor response has previously been shown to be due to the activation of the sympathetic nervous system and to the release of arginine vasopressin (AVP). The primary and secondary (AVP component) components of the pressor response were attenuated by 51 and 69%, respectively, by bilateral injections of procaine hydrochloride into PVH or bilateral electrolytic lesions of PVH. Control injections of saline into PVH or electrolytic lesions of hypothalamic regions anterior, dorsal, or ventral to PVH did not alter the ARN pressor response. These experiments demonstrate that sensory information originating in renal receptors excites magnocellular neurosecretory neurons in PVH and suggest that this renal-paraventricular reflex loop may contribute to the elevated arterial pressure and AVP release during conditions when ARN are activated.

Neuropeptide and serotonin immunoreactive neurons in the cat ventrolateral medulla.

The distribution of cell bodies containing serotonin (5-HT)-, substance-P (SP)-, neurotensin (NT)-, and somatostatin (SS)-like immunoreactivity (IR) in ventrolateral medulla (VLM) of the cat was studied immunohistochemically after administration of colchicine into the cisterna magna. Perikarya containing 5-HT-, SP-, NT- or SS-IR were found throughout the rostrocaudal extent of the VLM. Although neurons containing the different neuroactive substances appeared to have an overlapping distribution in VLM, some distinct differences were observed. In the caudal VLM most of the immunoreactive cell bodies observed contained 5-HT-IR. These neurons were found primarily in the region medial to lateral reticular nucleus (LRN) around the exiting intramedullary rootlets of the hypoglossal nerve (12N). In the intermediate region of VLM, perikarya containing 5-HT- and SP-IR were observed primarily near the ventrolateral surface of the medulla in the region around the exiting rootlets of the 12N. In contrast, most of the cells containing NT- and SS-IR were consistently observed to occupy a region in the medullary reticular formation immediately dorsal to that where 5-HT- and SP-IR perikarya were found. Finally, most of the immunoreactive perikarya were found in the rostral VLM; perikarya containing 5-HT- and SP-IR were observed throughout the nucleus paragigantocellularis lateralis (PGL) near the ventrolateral surface of the medulla. These data indicate that neurons immunoreactive to either 5-HT or several different neuropeptides were located in regions of VLM which have previously been implicated in the control of arterial pressure. As regions of VLM containing these neuroactive substances in neuronal perikarya have been shown to have direct connections with spinal sympathetic areas it is likely that these VLM cells are components of neuronal circuits involved in homeostatic mechanisms controlling the circulation.

Distribution and morphology of vasopressin-, neurophysin II-, and oxytocin-immunoreactive cell bodies in the forebrain of the cat.

Experiments were done to provide a detailed map of the location and a description of morphological characteristics of vasopressin (AVP-IR)-, neurophysin II (NII-IR)- and oxytocin (OXY-IR)-immunoreactive neuronal perikarya in the forebrain of the cat. In addition, the location of cells in the forebrain retrogradely labeled following injections of tracers into the neurohypophysis was determined. The distribution of AVP-IR and NII-IR was similar in all cases studied. Most of the cells containing AVP-IR and OXY-IR were observed in the hypothalamic paraventricular (PVH) and supraoptic (SON) nuclei. In addition, AVP-IR and OXY-IR cell bodies were found in the regions of the nucleus of the diagonal band of Broca, the dorsal chiasmatic nucleus, the anterior hypothalamic-preoptic area, the periventricular area, the nucleus circularis, the perifornical area of the lateral hypothalamus, the accessory SON, the area of the tuber cinereum (Tca), and the medial nucleus of the amygdala. The density of AVP-IR cells was greater than that of OXY-IR cells in these regions. Several forebrain areas were also observed to contain only AVP-IR perikarya: the suprachiasmatic nucleus (Sc), the bed nucleus of the stria terminalis, and the region of the substantia innominata and ventral globus pallidus (SI/GP). In addition, the dorsomedial nucleus of the hypothalamus only contained OXY-IR perikarya. Most of the cells immunoreactive to AVP were multipolar and had spinelike processes over their somata and proximal dendrites. In addition, the majority of cells in the PVH and SON were round or oval, whereas those outside these nuclei were fusiform or triangular. The mean somal area of AVP-IR cells in the region of the SI/GP was significantly (P less than 0.05) larger than that of AVP-IR cells in all other regions examined, whereas the mean somal area of Sc AVP-IR cells was significantly (P less than 0.05) smaller than that of all other groups of AVP-IR cells examined. Most OXY-IR cells were similar morphologically to those immunoreactive to AVP, except that OXY-IR cell bodies and their appendages did not have spinelike processes. In addition, OXY-IR perikarya were generally of uniform size. OXY-IR cells in the PVH and accessory SON were significantly (P less than 0.05) larger than AVP-IR cells in the same regions, but were not different from AVP-IR cells in the lateral hypothalamus and SON.(ABSTRACT TRUNCATED AT 400 WORDS)

Collateral branching in axonal projections to spinal cord from paramedian reticular nucleus neurons.

Experiments were done in cats to identify neurons in the paramedian reticular nucleus (PRN) sending collateral axons to the region of the intermediolateral nucleus (IML) at different levels of the thoracic cord by using lectin-conjugated horseradish peroxidase (HRP) and double-labeling fluorochrome histochemistry to retrogradely label PRN neurons. Injections of Fast blue (FB) into the spinal cord at the T2 level centered in the region of the IML were coupled with injections of Nuclear yellow (NY) into the ipsilateral cord at either the T4 or T7 levels centered in the region of the IML. Neurons in the PRN retrogradely labeled after diffusion of HRP into the region of the IML at the T2 level were observed throughout the rostrocaudal extent of the ventral PRN. In addition, a few labeled neurons were noted in the ventral portion of the dorsal PRN. About 40% of the neurons in the PRN which were labeled with FB after an injection at the T2 level were also labeled with NY injected into the cord in further caudal segments. These data suggest that the PRN may exert its influence on the cardiovascular system partly through collateral axonal branches to widely separated populations of sympathetic preganglionic neurons in different spinal segmental levels.

Effect of stimulation of afferent renal nerves on plasma levels of vasopressin.

Experiments were done in alpha-chloralose-anesthetized, paralyzed and artificially ventilated cats with vagus, cervical sympathetic, aortic depressor, and carotid sinus nerves cut bilaterally to investigate the effect of afferent renal nerve (ARN) stimulation on circulating levels of vasopressin (AVP). Electrical stimulation of ARN elicited a pressor response that had two components, a primary (1 degree) component locked in time with the stimulus and a secondary (2 degree) component that had a long onset latency and that outlasted the stimulation period. The 1 degree and 2 degree components of the pressor response were largest at stimulation frequencies of 30 and 40 Hz, respectively. Autonomic blockade with hexamethonium bromide and atropine methylbromide abolished the 1 degree component. Administration of the vasopressin V1-vascular receptor antagonist d(CH2)5VAVP during autonomic blockade abolished the 2 degree component. Plasma concentrations of AVP measured by radioimmunoassay increased from control levels of 5.2 +/- 0.9 to 53.6 +/- 18.6 pg/ml during a 5-min period of stimulation of ARN. Plasma AVP levels measured 20-40 min after stimulation (13.6 +/- 7.0 pg/ml) were not significantly different from control values. Plasma osmolality was not altered during the course of the experiment. These data demonstrate that sensory information originating in the kidney alters the release of vasopressin from the neurohypophysis and suggest that ARN are an important component of the neural circuitry involved in homeostatic mechanisms controlling arterial pressure.

Central organization of afferent renal nerve pathways.

Although afferent renal nerves have been studied for over a quarter of a century, their physiological role remains unclear. There is considerable experimental evidence indicating that afferent renal nerves convey sensory information from renal receptors to integrative circuits in the central nervous system which gives rise to command signals controlling the function of effector organs. In addition, it has been demonstrated that these integrative neural circuits are found at several different levels of the neuraxis; the spinal cord, the medulla and the hypothalamus. In this review, recent neuroanatomical and electrophysiological data on the central pathways of afferent renal nerves is discussed with reference to their possible role in homeostasis.

Function of the ventrolateral medulla in the control of the circulation.

The CNS control of the cardiovascular system involves the coordination of a series of complex neural mechanisms which integrate afferent information from a variety of peripheral receptors and produce control signals to effector organs for appropriate physiological responses. Although it is generally thought that these control signals are generated by a network of neural circuits that are widely distributed in the CNS, over the last two decades a considerable body of experimental evidence has accumulated suggesting that several of these circuits involve neurons found on or near the ventral surface of the medulla oblongata. Neurons in the VLM have been shown to be involved in the maintenance of vasomotor tone, in baroreceptor and chemoreceptor (central and peripheral) reflex mechanisms, in mediating the CIR and somatosympathetic reflexes and in the control of the secretion of vasopressin. These physiological functions of VLM neurons have been supported by neuroanatomical and electrophysiological studies demonstrating direct connections with a number of central structures previously implicated in the control of the circulation, including the IML, the site of origin of sympathetic preganglionic axons, and the SON and PVH, the site of origin of neurohypophyseal projecting axons containing AVP. Considerable suggestive evidence has also been obtained regarding the chemical messengers involved in transmitting information from VLM neurons to other central structures. There have been developments suggesting a role for monoamines and neuropeptides in mediating the neural and humoral control of SAP by neurons in the VLM. This review presents a synthesis of the literature suggesting a main role for VLM neurons in the control of the circulation.

Immunohistochemical identification of noradrenaline- and adrenaline- synthesizing neurons in the cat ventrolateral medulla.

The distribution and morphology of cell bodies containing the catecholamine biosynthetic enzymes dopamine-beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) in the ventrolateral medulla (VLM) of the cat were studied immunohistochemically after intracisternal administration of colchicine. Perikarya immunoreactive to DBH were found throughout the VLM extending from approximately the spinomedullary junction to the level of the superior olivary nucleus. In the caudal VLM DBH neurons were found primarily in the region immediately dorsal to the lateral reticular nucleus (LRN), although a few scattered DBH neurons were also found near the ventral surface of the medulla in and around the parvicellular division of the LRN. These DBH neurons in the caudal VLM were generally fusiform, fusiform-bipolar, or multipolar, with a mean somal area of 422 +/- 32 microns2, and with two to four branching processes. In the rostral VLM DBH neurons formed three distinct groups: one group was found in the nucleus paragigantocellularis lateralis in the region just ventromedial to the retrofacial nucleus (RFN) near the ventrolateral surface of the medulla; the second group was found in the region dorsomedial to the rostral aspects of the nucleus ambiguous and the RFN, and the third group was found in the region along the lateral aspect of the superior olivary nucleus. Perikarya immunoreactive to the adrenaline-synthesizing enzyme PNMT were localized to a more restricted region of the VLM that extended from approximately the rostral aspect of the caudal third of the inferior olivary complex (level of the obex) to the caudal pole of the facial nucleus. These PNMT neurons were fusiform or multipolar with a mean somal area of 273 +/- 21 microns2, and with two to five branching processes. The location, size, shape, and numbers of PNMT-immunoreactive neurons corresponded closely to the rostral groups of DBH neurons, with the exception of the group found along the lateral aspect of the superior olivary nucleus. These data indicate that noradrenaline-synthesizing neurons are primarily found in the caudal VLM and in the region near the superior olivary nucleus, whereas catecholamine neurons in the rostral VLM between these two noradrenergic cell groups synthesize adrenaline. As the VLM has previously been shown to have direct connections with spinal cord, brainstem, and hypothalamic areas implicated in cardiovascular and neuroendocrine regulation, this suggests that DBH- and PNMT-synthesizing neurons are components of neuronal circuits involved in these homeostatic mechanisms.

Bidirectional cardiovascular connections between ventrolateral medulla and nucleus of the solitary tract.

Single-unit recording experiments were done in chloralose-anesthetized, paralyzed and artificially ventilated cats to identify neurons in ventrolateral medulla (VLM) that send efferent axons directly to the region of the nucleus of the solitary tract (NTS) and receive cardiovascular afferent inputs from the carotid sinus (CSN) and aortic depressor (ADN) nerves and the NTS. Units in VLM were identified by antidromic excitation to stimulation of functionally and histologically verified sites in the NTS complex. Antidromic potentials were recorded from 34 units in VLM. Units responded with a mean antidromic latency of 4.37 +/- 0.32 ms corresponding to a mean conduction velocity of 0.93 +/- 0.07 m/s. Of these 34 units, 18 were excited orthodromically by stimulation of the CSN and/or ADN. Furthermore, 10 of the 18 units responding to stimulation of the buffer nerves were also orthodromically excited by stimulation of NTS. An additional 76 units were identified in VLM that only responded orthodromically to stimulation of NTS with a mean latency of 9.75 +/- 2.93 ms, of which 33 also responded orthodromically to stimulation of the buffer nerves. These data provide electrophysiological evidence of a bidirectional connection between neurons in VLM that receive and integrate peripheral cardiovascular afferent inputs and send efferent axons directly back to the region of NTS. These results suggest that neurons in the VLM may be part of a medullary feedback reflex loop through which afferent information from cardiovascular receptors exerts an influence on NTS neurons involved in the control of the circulation.

Lateral hypothalamic and peripheral cardiovascular afferent inputs to ventrolateral medullary neurons.

Experiments were done in chloralose anesthetized, paralyzed and artificially ventilated cats to identify single units in ventrolateral medulla (VLM) projecting directly to the intermediate gray (IG) region of the upper thoracic cord and responding to inputs from pressor sites in the anterior lateral hypothalamus (Hla) and carotid sinus (CSN) and aortic depressor (ADN) nerves. Forty-eight units were antidromically activated in VLM to stimulation of the IG at the level of T2. Of these 48 units, 15 (31%) were orthodromically excited by stimulation of the Hla with a mean latency of 15.8 +/- 2.1 ms. In addition, 8 of the 15 units responding to Hla stimulation were also excited orthodromically by stimulation of either the CSN or ADN or both. Of the remaining 33 units, 15 responded to stimulation of only the buffer nerves and 18 were unresponsive to the tested inputs. These results provide electrophysiological evidence for the existence of neurons in VLM which receive hypothalamic and buffer nerve inputs and suggest that the VLM plays a role in integrating and relaying cardiovascular afferent information from peripheral baroreceptors and chemoreceptors and from supramedullary centers to provide effector signals to spinal autonomic neurons involved in the control of the circulation.

Chemoreceptor and baroreceptor inputs to ventrolateral medullary neurons.

Recording experiments were done in chloralose-anesthetized, paralyzed, and artificially ventilated cats to identify single units in the ventrolateral medulla (VLM) projecting directly to the region of the intermediolateral nucleus of the spinal cord (T2) and responding to selective activation of peripheral chemoreceptors (sodium cyanide, 20-60 micrograms in 0.1-0.3 ml saline into medial thyroid artery) and baroreceptors (phenylephrine, 2 micrograms/kg iv). The firing frequency of 49 of the 81 antidromically identified single units was altered by activation of the peripheral cardiovascular receptors. Of these responsive units, 25 responded only to activation of chemoreceptors (17 excited and 8 inhibited), 20 responded in various combinations to activation of both chemo- and baroreceptors, and 4 responded only to activation of baroreceptors. In addition, units that altered their firing frequency during baroreceptor activation (n = 24) responded in the opposite direction to baroreceptor unloading (carotid arterial occlusion). These results suggest that neurons in the VLM are components of bulbospinal sympathoexcitatory and -inhibitory pathways that receive cardiovascular afferent information and in turn influence vasoconstrictor and cardioacceleratory neurons in the intermediolateral nucleus of the upper thoracic cord.

Lesions of the paraventricular nucleus alter the development of spontaneous hypertension in the rat.

The role of the paraventricular nucleus of the hypothalamus (PVH) in the development of hypertension was determined after bilateral electrolytic or sham lesions of this structure in 4-5-week-old male spontaneously hypertensive rats (SHR). The average arterial pressure in the PVH-lesioned group was significantly lower compared to sham-lesioned animals during the first 3 weeks after the PVH lesions. At 9 weeks of age the arterial pressures of the PVH-lesioned animals increased, but remained significantly lower than those of the sham-operated animals of the same age. This difference in arterial pressures was observed to 16 weeks of age. Heart rate was significantly reduced by PVH lesions up to 5 weeks after the lesions, at which point the heart rate tended towards the control values of the sham-lesioned animals. These data have demonstrated that the region of the PVH is important in the initial phase of the development of hypertension and in the full expression of the hypertension in the SHR, and provide evidence of a central mechanism in the hypertensive process in the SHR.

Electrophysiological identification of neurons in ventrolateral medulla sending collateral axons to paraventricular and supraoptic nuclei in the cat.

Experiments were done in chloralosed, paralyzed and artificially ventilated cats to identify single units in the ventrolateral medulla (VLM) that send collateral axons directly to the region of the paraventricular (PVH) and supraoptic (SON) nuclei, and responding to peripheral inputs carrying cardiovascular afferent information. Twenty-six single units were antidromically activated in the VLM to stimulation of both the PVH and SON, and in each case the antidromic potential evoked by stimulation of one site was cancelled by stimulation of the other site. These units responded with latencies corresponding to conduction velocities of 5.1 +/- 0.4 m/s. Of these 26 units, 10 responded orthodromically to stimulation of either the carotid sinus or aortic depressor nerves. These data have demonstrated the existence of VLM neurons which send collateral axons to the PVH and SON and have provided evidence for their role in mediating cardiovascular afferent information directly to hypothalamic regions involved in autonomic and neuroendocrine regulation.