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A V Ferguson

Publications and source records attributed to A V Ferguson.

At least 19 recordsLinked to original sources
PubMed1992

Angiotensin II actions in paraventricular nucleus: functional evidence for neurotransmitter role in efferents originating in subfornical organ.

Angiotensin II (ANG) has been suggested to be the neurotransmitter utilised by subfornical organ (SFO) efferents projecting to the paraventricular nucleus (PVN). The PVN has been shown to be involved in mediating the cardiovascular response elicited by electrical stimulation of SFO. The possible role of ANG as a neurotransmitter in these pathways has been examined in the present study. The cardiovascular effects of ANG microinjection into the PVN were examined in urethane anaesthetized, male Sprague-Dawley rats. Microinjection of 20 ng or 50 ng ANG into PVN resulted in mean increases in blood pressure of 12.8 +/- 0.6 mmHg (P < 0.0005), and 16.2 +/- 1.4 mmHg (P < 0.0001) respectively, without effect on heart rate. These responses were significantly attenuated following systemic administration of losartan, an ANG type 1 receptor (AT1) antagonist (Control, +12.8 +/- 0.6 mmHg; post-losartan, +5.6 +/- 1.7 mmHg), but were unaffected by the AT2 receptor antagonist, PD123319 (Control, +10.8 +/- 1.6 mmHg; post-PD123319, +11.6 +/- 2.4 mmHg). Initial and later components of the biphasic pressor response elicited by electrical stimulation of SFO (200 microA, 10 Hz, 1 ms pulse width, 10 s) were also significantly attenuated by losartan, but unaffected by PD123319. The short latency increase in mean arterial pressure was 16.6 +/- 2.3 mmHg in comparison to a post-losartan increase of 9.3 +/- 1.6 mmHg (P < 0.001). Similarly, the secondary response consisted of a control increase of 9.6 +/- 1.3 mmHg and a post-losartan increase of 3.4 +/- 0.9 mmHg (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1992

Endothelin acts at the subfornical organ to influence the activity of putative vasopressin and oxytocin-secreting neurons.

Systemic endothelin-1 (ET-1) enhances the activity of subfornical organ (SFO) neurons with identified projections to the paraventricular nucleus of the hypothalamus (PVN). The present electrophysiological experiments were undertaken to examine the mechanisms through which systemic ET influences vasopressin secretion. Systemic ET-1 (50-100 pmol) was found to influence the excitability of antidromically identified vasopressin and oxytocin-secreting neurons in the PVN or supraoptic nucleus (SON) of urethane-anaesthetized rats. Long-term stable recordings from 95 antidromically identified neurons showed 56% of putative vasopressin- (n = 41), and 37% of putative oxytocin- (n = 54) secreting neurons were activated by ET-1. Such effects normally demonstrated a short latency (less than 10 s), with a duration ranging between 10 and 300 s. In contrast, unidentified neurons in the vicinity of PVN and SON (n = 27) were unaffected by ET-1. The inability of peptides to cross the normal blood-brain barrier suggested that such effects of ET-1 result from actions of this peptide at the SFO which lacks this barrier and sends efferent neural projections to both SON and PVN. This hypothesis was tested by obtaining similar recordings from animals in which this structure was destroyed prior to experimentation. In these studies recordings from 15 putative vasopressin- and 29 putative oxytocin-secreting neurons showed that only 7% and 14%, respectively, were excited by systemic ET-1 in lesioned animals. These data show that increases in circulating levels of ET have predominantly excitatory effects on vasopressin- and oxytocin-secreting neurons in SON and PVN. The modified responsiveness of these neurons to ET-1 in SFO-lesioned animals suggests this as a likely CNS site at which this peptide acts within the central nervous system to elicit such effects.

Animals↗
PubMed1992

Actions of endothelin at the subfornical organ.

Endothelin (ET), a potent vasoconstrictor peptide, is believed to have central sites of action and potential neurohormonal effects relating to body fluid homeostasis and blood-pressure regulation. Systemic endothelin binds to receptors at circumventricular organs and has been shown to increase plasma concentrations of vasopressin and increase the firing frequency of neurohypophysial vasopressin and oxytocin neurons. In the present study we have examined the effects of ET on blood-pressure following micro-injection into the subfornical organ (SFO). Micro-injection of 0.5 and 5.0 pmol of endothelin into SFO caused significant increases (10.1 +/- 1.1 and 10.2 +/- 2.1, respectively) in blood pressure, while lower doses were without effect. In addition, we have used single unit recording techniques to evaluate the effects of systemic ET on the activity of SFO neurons. Extracellular recordings from SFO neurons, antidromically identified as projecting to PVN, showed predominantly excitatory responses to systemic ET (21/35 cells). The data demonstrate that ET has excitatory actions on SFO neurons, and further raise the possibility that one of the functional consequences of such effects is an increase in arterial blood pressure.

Animals↗
PubMed1992

Central actions of angiotensin in cardiovascular control: multiple roles for a single peptide.

Angiotensin II (ANG II) acts peripherally as a hormone, with actions on the vasculature, adrenals, and kidney. In addition, certain actions of ANG II in the central nervous system are directed toward cardiovascular control and fluid volume homeostasis. Dense binding sites for ANG II are found at circumventricular organs, which apparently have the ability to relay information to cardiovascular centers via neural circuitry. Microinjection of ANG II into the subfornical organ (SFO) or area postrema (AP) produces site-specific increases in blood pressure. In addition, electrophysiological studies demonstrate profound effects of ANG II, acting at the SFO, on activity of neurohypophysial neurons and release of oxytocin and vasopressin, which can be antagonized by ANG II blockers or attenuated by SFO lesions. Evidence from microinjection, electrophysiological, and lesion studies indicate a complex interaction between central sites involved in mechanisms of cardiovascular control: the SFO, AP, organum vasculosum of the lamina terminalis, and paraventricular and supraoptic nuclei of the hypothalamus. Not only is ANG II a humoral messenger in this central scenario, but evidence suggests it acts as a neurotransmitter or neuroendocrine substance within specific CNS pathways, suggesting multiple roles for this peptide in central cardiovascular control.

Angiotensin II↗
PubMed1992

Neurally mediated gastric mucosal damage in hypophysectomized rats.

The role of the pituitary hormones in the development of neurally mediated gastric mucosal damage was examined in both normal and hypophysectomized urethane-anaesthetized male Sprague-Dawley rats. Gastric mucosal damage was elicited either by electrical stimulation of intact vagal nerves or by electrical stimulation in the paraventricular nucleus. Macroscopic damage was scored following the stimulation period and samples of the stomach were fixed for histological assessment. Damage scores were assigned based on a 0 (normal) to 3 (severe) scale. Control experiments in which the vagi were not stimulated did not result in any significant gastric damage in either normal (0.56) or sham surgery (0.14) animals, whereas hypophysectomized animals were observed to have significant damage (1.44, p < 0.05). Stimulation of the vagi in hypophysectomized animals resulted in damage that was not significantly different compared with the hypophysectomized control animals (1.25, p > 0.05). In normal animals, stimulation of vagal nerves resulted in mean damage scores of 2.00, values that were not significantly different from those observed in hypophysectomized animals (1.25, p > 0.05). Similarly, stimulation in the paraventricular nucleus of hypophysectomized animals resulted in gastric lesions (2.00) that were not significantly different from those observed in normal animals (1.91, p > 0.05). These data suggest that such neurally mediated gastric damage does not depend upon neurosecretory projections to the pituitary gland, but that the maintenance of an intact gastric mucosa under normal conditions requires the presence of pituitary hormones.

Animals↗
PubMed1991

Circulating endothelin influences area postrema neurons.

The recently described endothelium-derived constricting factor endothelin (ET) is a 21 amino acid peptide which is the most potent endogenous vasoconstrictor yet described. Binding sites for this peptide have been demonstrated within the circumventricular structures of the brain. One of these structures, the area postrema (AP), has been implicated in central cardiovascular control mechanisms. We have recently demonstrated that microinjection of ET into this structure results in dose-dependent changes in mean arterial blood pressure. The present studies were undertaken to test the hypothesis that ET elicits these effects as a result of influences on the activity of AP neurons. Using extracellular single unit recording techniques we have examined the effects of systemic administration of ET on the activity of AP neurons. A total of 60 AP neurons were tested for effects of ET (0.1-10.0 pmol) of which the spontaneous activity of 32 showed rapid (modified frequency of action potentials in the 60s following ET), reversible (return to baseline activity within 10 m) responses to this peptide. The initial response of the majority (84%) of AP neurons influenced by ET was excitatory, while a smaller proportion of AP neurons were inhibited (16%) by systemic administration of this peptide. We have also examined whether such excitatory effects were specific to AP neurons by comparing the above response characteristics to those observed in neurons in the adjacent commissural NTS. Such recordings demonstrated predominantly inhibitory (84% of influenced cells) responses of this group of NTS neurons to ET. While these findings demonstrate specific excitatory effects of systemic ET on the activity of AP neurons they also suggest a potential role for this peptide in controlling the activity of NTS neurons. These studies provide evidence that circulating ET influences AP neuronal function, although they offer no definitive information as to the specific site of action.

Action Potentials↗
PubMed1991

Effects of parabrachial stimulation on angiotensin and blood pressure sensitive area postrema neurons.

Subpopulations of neurons in the area postrema (AP) and commissural nucleus tractus solitarius (NTS) have been identified according to their responses to systemic angiotensin-II (ANG-II) and increases in blood pressure (BP). In order to further define the functional connections of these subpopulations of cells, electrophysiological single unit recording studies have been done to determine the orthodromic effects of parabrachial nucleus (PBN) stimulation on these functionally defined cell groups. Orthodromic effects were seen in a similar proportion of ANG-II sensitive neurons in the AP (31.5%) and NTS (31%). PBN stimulation influenced a similar percentage of BP sensitive neurons in the AP (35%), although a larger proportion of this group of NTS cells was affected (55.5%). Twenty-five percent of ANG-II/BP sensitive neurons in the AP were orthodromically influenced, and 71.5% of this group of NTS neurons were affected by PBN stimulation. Small proportions of the neurons in the unaffected subpopulation of AP (10%) and NTS (27%) were also orthodromically affected by PBN stimulation. The remaining neurons in each group were not affected. This study suggests that there is no apparent preferential distribution of excitatory or inhibitory PBN efferents to any of the identified subpopulations of AP and NTS neurons.

Angiotensin II↗
PubMed1991

The area postrema: a cardiovascular control centre at the blood-brain interface?

The area postrema (AP) is one of the circumventricular organs of the brain and as such it is highly vascular and lacks the normal blood-brain barrier. Anatomical tracing studies have demonstrated afferent projections to AP originating from the paraventricular nucleus, lateral parabrachial nucleus (l-PBN), nucleus tractus solitarius (NTS), as well as the vagus nerve. AP neurons have been shown to project primarily to l-PBN, and NTS. Receptor localization studies have reported dense aggregations of many specific peptide receptors in AP including those for angiotensin II (ANG), atrial natriuretic peptide (ANP), and endothelin (ET). Electrical stimulation studies have shown that activation of AP neurons at low frequencies (less than 15 Hz) results in decreases in blood pressure and heart rate, while higher frequency (greater than 20 Hz) stimulation causes increases in blood pressure. These low frequency effects on blood pressure and heart rate appear to result from activation of separate components of the autonomic nervous system. Extracellular single unit recordings have identified two functionally separate populations of AP neurons: one responsive to circulating ANG and a second apparently responsive to changes in blood pressure. In addition, AP neurons are activated by increases in circulating ET. Afferent inputs to AP neurons from 1-PBN have separate excitatory (12% of AP neurons) or inhibitory (12% of AP neurons) effects on a relatively small proportion of AP neurons. In contrast, preliminary evidence suggests a much more broadly distributed excitatory input to approximately 70% of tested AP neurons originating from the aortic depressor nerve. These studies provide considerable evidence implicating the AP as a significant neural structure regulating the cardiovascular system.

Animals↗
PubMed1991

Vagal stimulation-induced gastric damage in rats.

The role of the vagus nerve in the development of gastric mucosal damage was examined in urethan-anesthetized male Sprague-Dawley rats. Electrical stimulation was applied to the vagus nerves for a period of 60 min, after which macroscopic gastric damage was scored and samples of the stomach were fixed for later histological assessment. Damage scores were assigned blindly based on a 0 (normal) to 3 (severe) scale. Stimulation of vagal afferents or efferents in isolation did not result in significant damage to the gastric mucosa (P greater than 0.1). In contrast, stimulation of both intact vagus nerves resulted in significant gastric mucosal damage (mean damage score, 2.0 +/- 0.33, P less than 0.01). A second series of experiments demonstrated this gastric damage to be induced within 30-60 min; extending the stimulation period to 120 min did not worsen the gastric damage scores significantly (P greater than 0.1). In a third study, stimulation of both intact vagus nerves after paraventricular nucleus (PVN) lesion resulted in damage scores (0.33 +/- 0.17) that were significantly reduced compared with intact PVN and non-PVN-lesioned animals (P less than 0.01). These results indicate that the development of vagal stimulation-induced gastric damage requires the activation of both afferent and efferent vagal components and suggest further that such damage is dependent upon an intact PVN.

Animals↗
PubMed1991

Autonomic mechanisms underlying area postrema stimulation-induced cardiovascular responses in rats.

Experiments were designed to examine the autonomic mechanisms underlying the decreases in blood pressure and heart rate elicited by electrical stimulation in the rat area postrema (AP). Vagotomy was found to significantly reduce the bradycardia observed in response to AP stimulation (control -123.5 +/- 23.5 beats/min; vagotomized -7 +/- 5.4 beats/min; P less than 0.001) but was without significant effect on blood pressure responses. Hexamethonium significantly reduced both heart rate (control -225.5 +/- 11.9 beats/min; hexamethonium -5.5 +/- 2.8 beats/min; P less than 0.001) and depressor (control -35.4 +/- 4.7 mmHg; hexamethonium -6.4 +/- 0.8 mmHg; P less than 0.001) responses to such stimulation, whereas combined alpha- and beta-adrenergic blockade was without effect. The muscarinic blocking agent atropine also abolished both blood pressure (control -22.0 +/- 4.3 mmHg; atropine 2.8 +/- 4.4 mmHg; P less than 0.01) and heart rate (control -187.0 +/- 41.9 beats/min; atropine 8.8 +/- 2.6 beats/min; P less than 0.01) responses to AP stimulation. These data suggest that AP stimulation influences two separate neural pathways eliciting distinct cardiovascular responses. It would appear that activation of one of these pathways results in activation of vagal efferents to the heart and thus bradycardia. A second parallel pathway influenced by AP stimulation apparently elicits depressor response through actions on cholinergic muscarinic receptors.

Animals↗
PubMed1991

Electrophysiological evidence of baroreceptor input to area postrema.

Subpopulations of rat area postrema (AP) and nucleus tractus solitarius (NTS) neurons exist that are responsive to changes in blood pressure. The hypothesis that these effects may be mediated by afferent baroreceptor input was examined. Orthodromic responses of AP and NTS neurons to aortic depressor nerve (ADN) stimulation were observed. Sixty-three percent of AP neurons were affected by ADN stimulation, with most exhibiting short-duration excitatory responses (latency, 27 +/- 1 ms; duration, 11 +/- 1 ms). Fifty-five percent of NTS neurons were influenced by ADN stimulation, although effects in this region were more heterogeneous (24% of neurons excited, 31% inhibited). Thus, in the rat, apparently both AP and NTS neurons receive afferent barosensory information.

Afferent Pathways↗
PubMed1990

Cardiovascular responses induced by endothelin microinjection into area postrema.

The recently described endothelium derived constricting factor endothelin (ET) is a 21 amino acid peptide which is the most potent endogenous vasoconstrictor yet described. Binding sites for this peptide have been demonstrated within the circumventricular structures of the brain. One of these structures, the area postrema (AP), has been implicated in central cardiovascular control mechanisms. We have therefore examined the effects of AP microinjection of ET on blood pressure in urethane-anaesthetised rats. Such treatment resulted in dose-dependent biphasic changes in arterial blood pressure (increases followed by decreases). Low doses of ET (0.2-1.0 pmol) induced significant increases (P less than 0.01), and high doses (5.0 pmol) significant decreases (P less than 0.01), while at intermediate concentrations (2.0 pmol) ET caused significant increases (P less than 0.05) followed by significant decreases (P less than 0.01) in mean blood pressure. Other vasoconstrictors were found to be without effect following AP administration, suggesting these changes to be the result of specific action of ET. In contrast, both ET and methoxamine had similar cardiovascular actions when microinjected into regions anatomically adjacent to the AP such as the NTS, indicating that vasoconstriction in these areas induces changes in femoral arterial blood pressure. These data suggest a specific role for ET as a chemical messenger involved in central nervous system control of the cardiovascular system within AP.

Animals↗
PubMed1990

Electrophysiological characterization of reciprocal connections between the parabrachial nucleus and the area postrema in the rat.

Neuroanatomical studies have demonstrated reciprocal connections between the parabrachial nucleus (PBN) and both the area postrema (AP) and the nucleus tractus solitarius (NTS). To functionally characterize these projections, antidromic identification of AP and NTS neurons projecting to the PBN was attempted. Orthodromic influences on these cells, resulting from PBN stimulation, were also examined. Four percent of AP neurons tested (n = 74) were antidromically identified as projecting to the PBN [latency (L) = 26 +/- 4 msec, threshold current (T) = 79 +/- 11 microA]. Parabrachial stimulation orthodromically influenced 24% of AP cells. Equal numbers of these neurons (12%) were excited [L = 25 +/- 9 msec, duration (D) = 29 +/- 14 msec] and inhibited (L = 28 +/- 8 msec, D = 107 +/- 40 msec). Of 46 NTS neurons tested, 11% were antidromically identified as projecting to the PBN (L = 12 +/- 4 msec, T = 61 +/- 18 microA), while orthodromic influences were seen in 41% of these neurons. Initial responses of 30% of the cells were excitatory (L = 34 +/- 14 msec, D = 63 +/- 24 msec), PBN stimulation inhibited the remaining 11% of NTS neurons (L = 30 +/- 10 msec, D = 108 +/- 32 msec). These findings suggest that a functional heterogeneity exists in the PBN efferents to the AP and NTS. However, the small proportion of antidromically identified AP and NTS efferents to the PBN disagrees with neuroanatomical studies suggesting a denser projection.

Animals↗
PubMed1990

Electrophysiological evidence that systemic angiotensin influences rat area postrema neurons.

Extracellular single-unit recordings from neurons in the area postrema (AP) and the nucleus tractus solitarius (NTS) in anesthetized male rats demonstrated that most cells in these regions have spontaneous activities of 5 Hz or less. Systemic angiotensin (ANG II) (50-500 ng) enhanced the activity of 55% of AP cells tested (n = 76), whereas 53% of tested NTS neurons (n = 62) were inhibited by ANG II. To determine whether these neurons were influenced specifically by circulating ANG II or by the accompanying increase in mean arterial blood pressure (BP), the effects of adrenergic agonists given intravenously on ANG II influenced neurons were also examined. Subsequently two cell types were characterized: cells responding to iv ANG II but not to the adrenergic agonist ("ANG II sensitive") and cells responding in a similar way to both agents ("BP sensitive"). Most ANG II-responsive neurons in the AP (53.5%) and the NTS (65%) were determined to be BP sensitive. These data demonstrate that ANG II influences the activity of AP neurons. In addition, there exists a second population of AP neurons apparently responsive to perturbations of the cardiovascular system. These studies further emphasize the potential roles of the AP in the regulation of body fluid balance.

Angiotensin II↗
PubMed1990

Metabolic activation of efferent pathways from the rat area postrema.

We used the quantitative [14C]deoxyglucose method and autoradiography to evaluate metabolic activity in 47 individual cerebral structures or subregions that are part of neural pathways emanating from the brain stem circumventricular organ, area postrema. Electrical stimulation of the dorsocentral area postrema in halothane-ventilated rats produced hypotension and increased glucose metabolism by several structures within the ascending trajectories of efferent neural projections from the nucleus. Structures in the caudal medulla oblongata, including three subnuclei of the nucleus of the solitary tract, dorsal motor nucleus of the vagus nerve, and nucleus ambiguus-A1 noradrenergic region, had increases of metabolism during stimulation of 32-62%. Pontine activation occurred specifically in the locus coeruleus and lateral parabrachial nuclei (increases of 24-36%). Magnocellular and parvocellular subdivisions of the hypothalamic paraventricular nucleus, supraoptic and suprachiasmatic nuclei, and median eminence showed increases in metabolism of 22-34%. An 89% elevation of glucose metabolism by the pituitary neural lobe resulted. The findings are evidence for functional activation of specific structures within ascending neural pathways from area postrema to forebrain mechanisms regulating blood pressure and fluid balance.

Animals↗
PubMed1990

Circumventricular structures: CNS sensors of circulating peptides and autonomic control centres.

Previous studies have suggested the subfornical organ (SFO) to be the CNS site at which circulating angiotensin (ANG) acts to influence a variety of regulatory control mechanisms. We have utilised electrophysiological techniques: 1. to examine the neural connections through which the SFO exerts such control over hypothalamic regulatory control centres; 2. to investigate the responsiveness of neurons in a second circumventricular organ, the area postrema (AP), to circulating peptides. In accordance with previous endocrine studies we have demonstrated excitatory influences of SFO efferents on hypothalamic neurosecretory neurons putatively identified as vasopressin, oxytocin, CRH, and LHRH secreting. In addition systemic ANG increased the activity of the former three groups of these neurons, an effect which was abolished by destruction of the SFO. Single unit recordings from AP neurons have demonstrated subpopulations of cells in this regions to be sensitive to either circulating ANG or changes in blood pressure.

Angiotensin II↗
PubMed1989

Subfornical organ activation stimulates luteinizing hormone secretion in the rat.

The effect of electrical stimulation in the subfornical organ (SFO) on plasma luteinizing hormone (LH) concentrations has been examined in the conscious freely moving male Sprague-Dawley rat. Plasma LH levels were significantly elevated above basal levels 15 min following stimulation in the SFO. In contrast, stimulation in the adjacent hippocampal commissure caused no significant change in plasma concentrations of LH. These results correlate well with previous electrophysiological studies demonstrating that SFO stimulation activates putative LH-releasing hormone (LH-RH) containing neurons in the septum which project to the median eminence and add further support to the hypothesis that the SFO plays a significant role in the control of reproductive function.

Animals↗