Biomedical subjects

A V Ferguson

Publications and source records attributed to A V Ferguson.

At least 19 recordsLinked to original sources

PubMed1996

Whole cell patch recordings from forebrain slices demonstrate angiotensin II inhibits potassium currents in subfornical organ neurons.

Whole cell patch clamp recordings have been obtained from SFO neurons in a forebrain slice preparation. Basic electrophysiological characteristics recorded from these cells in current clamp mode showed a mean resting membrane potential of -57.0 +/- 2.5 mV (+/- SEM, n = 7), mean input resistance of 900 +/- 110 M omega (n = 7), and a mean spike amplitude of 68.6 +/- 4.1 mV (n = 7), accompanied by either irregular or no spontaneous activity. All cells also demonstrated a delayed return to baseline membrane potential following large hyperpolarizing current pulses indicative of the presence of a rapidly activated transient potassium current in these neurons. Voltage clamp recordings identified both rapid transient, and a sustained outward currents which demonstrated the characteristics of IA and IK respectively. While bath administration of angiotensin II (Ang) (10(-7) M) was without effect on IK in 4 of 4 neurons tested, IA was reduced by between 20 and 100% in the same 4 neurons. These data provide the first description of the basic electrophysiological characteristics of SFO neurons recorded in forebrain slice preparations. They also provide the first direct evidence suggesting that Ang may exert its control over the excitability of SFO neurons through modulation of IA in these cells.

Angiotensin II↗

PubMed1996

Angiotensin II and glutamate influence area postrema neurons in rat brain slices.

The area postrema (AP) has been repeatedly implicated in cardiovascular regulation. Microinjection and single unit recording studies in vivo have suggested specific actions for angiotensin II (ANG) and glutamate (GLU) in controlling the excitability of AP neurons. The present study was therefore designed to examine the responsiveness of AP neurons to bath administration of these substances. Of the 133 AP neurons tested with ANG (10(-8)-10(-6) M) 40% were excited, 13% inhibited and the remainder unresponsive. The excitatory effects of ANG on AP neurons were dose-dependent. Following blockade of synaptic transmission with a low calcium high magnesium solution excitatory responses were maintained in 12 of 15 cells tested. Pretreatment of slices with the AT1 receptor antagonist losartan blocked the excitatory effects of ANG in all cells (5/5) tested. The effects of GLU on AP neurons were also examined. Of the 71 AP cells tested, 40% were excited, 10% inhibited, 8% showed excitatory responses followed by periods of inhibition while the remaining cells were unaffected. Excitatory effects of GLU were maintained in all AP neurons (7/7) tested during perfusion with low calcium, high magnesium solutions. Similar responses to NMDA were observed in four of four cells tested, suggesting these GLU actions are mediated through NMDA receptors. These data demonstrate direct excitatory actions of ANG and GLU on AP neurons which are likely mediated through the AT1 and NMDA receptors, respectively.

Angiotensin II↗

PubMed1996

Electrophysiology of the circumventricular organs.

Since the first anatomical description of the circumventricular organs (CVOs) as a structurally distinct group of regions in the central nervous system (CNS), considerable information has implicated these structures as physiologically significant autonomic control centers located at the blood-brain interface. Specialized features of these structures, such as their extensive vasculature, lack of the normal blood-brain barrier (BBB) (i.e., capillaries have a fenestrated endothelium), and dense aggregations of a variety of peptidergic receptors, support an involvement of the CVOs in communication between the circulation and the CNS. The two best understood examples of CVOs with the ability to sense circulating substances impermeable to the BBB are the subfornical organ (SFO) and the area postrema (AP). Specifically, the ability of numerous peptides to influence CNS function, as the result of actions on the neural substrate of these structures has been especially well documented. Considerable anatomical, biochemical, pharmacological, and physiological evidence has implicated these structures as CNS sites at which angiotensin (ANG), atrial natriuretic peptide (ANP), vasopressin (VP), and endothelin (ET) act to influence neuroendocrine and other more classical autonomic functions. In the following sections, we review neurophysiological studies which have provided new and exciting insights regarding the specific neural pathways and cellular mechanisms through which CVO neurons are able to exert their profound influences over central autonomic control.

Animals↗

PubMed1996

Electrophysiological properties of paraventricular magnocellular neurons in rat brain slices: modulation of IA by angiotensin II.

Whole-cell patch-clamp recordings obtained from magnocellular neurons of the hypothalamic paraventricular nucleus in brain slice preparations of adult Sprague-Dawley rats have been utilized to examine three outward potassium conductances and the ionic mechanisms through which angiotensin II exerts its neurotransmitter actions within this region. Lucifer Yellow fills showed that neurons from which we recorded had large ovoid cell bodies 11-17 microns wide and 22-35 microns long, as well as 1-3 minimally branched processes, anatomical features in accordance with those previously described for magnocellular neuroendocrine neurons. These neurons had an average resting membrane potential of -58.3 +/- 0.9 (mean +/- S.E.M.) mV, spike amplitude of 92.8 +/- 1.4 mV, and input resistance of 788.9 +/- 50.4 M omega. Most of these cells displayed irregular or continuous spontaneous activity with a mean frequency of 2.44 +/- 0.33 Hz. Voltage-clamp recordings revealed three outward potassium currents; (1) a delayed outward current (IK), (2) a Ca(2+)-dependent outward current (IK(Ca)) and (3) a transient outward current (IA). These currents were classified according to their voltage dependence, inactivation, Ca2+ dependence and pharmacology. The IK was activated by depolarization beyond -40 mV and its amplitude consistently increased with depolarizing steps. The membrane conductance underlying this current was 27.3 +/- 3.8 nS for depolarization to +50 mV. In medium containing 2 mM Ca2+, depolarization to above -20 mV evoked a slowly-activating IK(Ca) which showed minimal inactivation. This current was suppressed in Ca(2+)-free/Co2+ medium and its membrane conductance was also smaller (19.4 +/- 3.5 nS at +50 mV) than that of IK. The IA demonstrated both fast activation and inactivation and was evoked only if depolarizing pulse steps were preceded by conditioning hyperpolarization. The activation threshold was approximately -65 mV and IA amplitude increased in non-linear fashion as test voltage steps became more positive. The 90% maximum of IA conductance was 15.7 +/- 1.1 nS, and was observed at membrane potentials around -15 mV. The reversal potentials of these currents were in accordance with the K+ equilibrium potential. Tetra-ethylammonium reversibly inhibited both the peak and steady-state currents of the IK, while 4-aminopyridine suppressed the IA. Replacement of 2 mM Ca2+ with 2 mM Co2+ in our bath solution or addition of Co2+ into Ca(2+)-free medium reduced the magnitude of IA, revealing the existence of a Co(2+)-sensitive IA. Bath administration of 10(-7) M angiotensin was without significant effect on IK, but resulted in a statistically significant reduction in IA (-31.0 +/- 4.1%) in 12 of 14 paraventricular nucleus cells tested, effects which were not observed following pretreatment with the AT1 receptor antagonist losartan. We conclude that in paraventricular nucleus magnocellular cells, like other CNS neurons, at least three sets of potassium channels contribute to the outward current evoked by depolarization. Our data also demonstrate ionic mechanisms through which angiotensin may act at AT1 receptors to influence the excitability of hypothalamic neuroendocrine cells.

Angiotensin I↗

PubMed1996

Paraventricular nucleus efferents influence area postrema neurons.

Extracellular single-unit recordings were obtained from area postrema neurons (AP), and peristimulus histograms were used to determine the effects of paraventricular nucleus (PVN) stimulation on these cells from anesthetized Sprague-Dawley rats. Of 91 AP cells tested, 30.8% responded to PVN stimulation with a short-latency (28.2 +/- 3.3 ms, mean +/- SE), short-duration (49.3 +/- 8.0 ms) excitation, whereas 8.6% were inhibited. In animals that had stimulation sites outside of PVN (non-PVN), only 4 of the 72 AP cells tested (5.6%) were influenced by stimulation. These excitatory effects of PVN stimulation on AP neurons were unaffected by V1-receptor blockade. Of 93 nucleus of the solitary tract (NTS) cells tested, 38.9% responded to PVN stimulation with a short-latency (18.5 +/- 2.4 ms), short-duration (48.8 +/- 9.6 ms) excitation and 22.2% with short-latency (20.75 +/- 4.1 ms), long-duration (204.4 +/- 44.9 ms) inhibitions. In contrast, non-PVN stimulation sites influenced only 19% of NTS neurons tested, all of which were excited. These data demonstrate that activation of PVN neurons elicits excitatory effects on the majority of AP neurons influenced. They further emphasize the potential significance of descending hypothalamic inputs in controlling neuronal activity in this circumventricular organ.

Animals↗

PubMed1996

In vitro recordings from area postrema neurons demonstrate responsiveness to adrenomedullin.

Adrenomedullin (ADM) is a recently discovered 52-amino acid peptide that exerts potent vasodilatory effects in the periphery and influences the control of body fluid balance when injected centrally. In this study extracellular single-unit recordings were obtained from 94 AP neurons in rat brain slices. Bath application of ADM (10(-7) M) excited 47% (32 of 68) of cells tested, and these effects were found to be dose dependent from 10(-7) to 10(-9) M. Excitation was maintained during synaptic blockade in a low-Ca2+ artificial cerebrospinal fluid solution, demonstrating direct actions of ADM on these neurons. The remaining cells were either unaffected (n = 25) or inhibited (n = 11) by ADM. ADM (10(-7) M) also influenced the spontaneous activity of 9 (7 inhibited, 2 excited) of 16 neurons located in the nucleus tractus solitarii (NTS). However, these effects could be eliminated during synaptic blockade, suggesting indirect actions of the peptide on NTS neurons. These data demonstrate that a specific population of CNS neurons within the AP are directly influenced by ADM and suggest that ADM may exert its effects on the central control of fluid balance through direct actions at this circumventricular organ.

Adrenomedullin↗

PubMed1995

Subfornical organ stimulation elicits drinking.

The subfornical organ is a specialized central nervous system structure known to be involved in the control of drinking. We report here that electrical activation of subfornical organ neurons (100 microA, 10 Hz, 1 ms pulse width, for 5 min.) induced drinking in 67% (six of nine) of animals. This effect was site-specific as none of the animals with electrode placements (n = 7) dorsal or rostral to the subfornical organ drank in response to electrical stimulation. In contrast, activity levels were increased significantly during stimulation in both the subfornical and nonsubfornical organ stimulated groups. These results suggest that electrical stimulation of the subfornical organ can elicit site-specific drinking behaviour and provide further support for the involvement of the subfornical organ in the control of drinking behaviour.

Animals↗

PubMed1995

Paraventricular nucleus neurons projecting to the spinal cord receive excitatory input from the subfornical organ.

The present study utilized electrophysiological techniques to determine the effects of subfornical organ (SFO) stimulation on the activity of neurons in the paraventricular nucleus (PVN) projecting to the spinal cord. Single-unit recordings were obtained from 79 PVN neurons antidromically identified as projecting to the intermediolateral cell column (IML). Antidromically evoked action potentials showed a mean latency of 94.6 +/- 5.3 ms and a mean threshold for activation of 1.58 +/- 0.11 mA. Electrical stimulation of SFO (100 microA-1.5 mA, 0.1 ms) resulted in excitatory responses in 18 of the 27 neurons tested (67%). Peristimulus histogram analysis of such effects demonstrated a duration of < 50 ms in 14 of the 18 cells so influenced (78%), whereas the remaining 4 cells (22%) showed excitatory responses with a longer duration. Systemic administration of the nonpeptidergic angiotensin II (ANG) type 1 (AT1) receptor antagonist losartan (3 mg/kg) blocked the long-duration excitatory responses in 100% (3 of 3) of the cells tested but was without effect on the short-duration excitations (0 of 5). Twenty-two identified PVN neurons were also tested for their responses to systemic ANG (20-500 ng), which had no observable effect on the activity of any of these cells. These data demonstrate that neurons in SFO provide excitatory input to PVN cells that project to the IML. One of the neurotransmitters responsible for communication in this pathway is ANG.

Angiotensin Receptor Antagonists↗

PubMed1995

Vasopressin actions on area postrema neurons in vitro.

The area postrema (AP) is a circumventricular organ located on the dorsal surface of the medulla. Substantial evidence suggests that the AP is an important site involved in cardiovascular regulation. Arginine vasopressin (AVP) is thought to act at the AP to increase the sensitivity of the baroreceptor reflex. We have therefore examined the effects of AVP on AP neurons with the use of extracellular single unit recordings in vitro. Coronal medullary brain slices (thickness = 400 microns) were obtained from male Sprague-Dawley rats and maintained in oxygenated artificial cerebrospinal fluid (aCSF). The slices were perfused with AVP (10(-8) to 10(-6) M), and the effect on single AP neurons was recorded. A total of 79 AP neurons was tested of which 50 (63.3%) were excited by AVP and 5 (6.3%) were inhibited, whereas the remaining 24 (30.3%) cells were unaffected. The excitatory effects of AVP were dose dependent: firing rate increased 92.6 +/- 25.8% at 10(-8) M, 289.4 +/- 53.9% at 10(-7) M, and 456.8 +/- 113.1% at 10(-6) M, respectively. We also examined whether these effects of AVP resulted from direct actions of this peptide on AP cells by testing if responses were retained during blockade of synaptic transmission (achieved by perfusion with a low Ca(2+)-high Mg2+ aCSF) in 11 cells excited by AVP. Nine of these cells were excited by AVP during such synaptic blockade. Finally, we demonstrated that the excitatory responses of five AP cells to AVP were all totally abolished by perfusion of slices with aCSF containing the V1 antagonist ([1-beta-mercapto-beta,beta-cyclopentamethylene propionic acid,2-(O-methyl)tyrosine]-Arg8-vasopressin; Peninsula Laboratories, 10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Modified cardiovascular sensitivity of the area postrema to vasopressin in spontaneously hypertensive rats.

Vasopressin has been shown to act at the area postrema to increase the sensitivity of the baroreceptor reflex. We have previously demonstrated that microinjection of vasopressin into the area postrema of Sprague-Dawley rats elicits pressor effects. We report here that vasopressin microinjection into the area postrema of spontaneously hypertensive rats is without effect on blood pressure, whereas microinjection into age-matched Wistar-Kyoto controls results in significant increases in blood pressure at 50 and 100 pg. These results suggest an altered sensitivity of the area postrema to vasopressin in this genetic model of hypertension.

Animals↗

PubMed1994

Angiotensin II neurotransmitter actions in paraventricular nucleus are potentiated by a nitric oxide synthase inhibitor.

There is increasing evidence that nitric oxide (NO) plays a role within the central nervous system as a novel messenger. Neuronal culture work suggests NO to be involved specifically in mediating actions of angiotensin II (ANG). The present study examined the potential role of NO within the paraventricular nucleus (PVN), a structure involved in mediating the cardiovascular changes initiated by activation of the subfornical organ (SFO). The pressor response to stimulation of SFO, which can be divided into a short (SD) and long duration (LD) component was enhanced following administration of an NO synthase inhibitor (L-NAME) (SD control: 101 +/- 4 vs. post L-NAME: 145 +/- 10 mmHg.s (P < 0.05); LD control: 387 +/- 167 vs. post L-NAME: 1737 +/- 617 mmHg.s (P < 0.05)). This effect was specific to activation of SFO efferents as the blood pressure responses to either, stimulation of PVN, or systemic administration of vasopressin were not potentiated by administration of L-NAME. These findings suggest that NO may be acting within PVN to inhibit further release of ANG, thereby attenuating the cardiovascular response to stimulation of SFO.

Amino Acid Oxidoreductases↗

PubMed1994

Circulating vasopressin influences area postrema neurons.

Extracellular single-unit recordings were obtained from 107 area postrema and 74 nucleus tractus solitarius neurons in sodium pentobarbital anaesthetized rats. Systemic administration of vasopressin (1-10 ng) decreased the firing frequency of 45.8% of area postrema neurons and 58.1% of nucleus tractus solitarius neurons tested while the firing frequency of 38.3% of area postrema neurons and 21.6% of nucleus tractus solitarius neurons was increased by this peptide. To determine whether these neurons were specifically influenced by vasopressin or the accompanying pressor response, the effects of alpha-adrenergic agonists on neuronal activity were also determined. Cells that responded similarly to vasopressin and the change in blood pressure elicited by alpha-adrenergic agonists were classified as "blood pressure-sensitive", whereas those neurons that responded differently to both agents were classified as "vasopressin-sensitive" neurons. The majority (85.2%) of area postrema cells that decreased firing frequency in response to vasopressin were determined to be "vasopressin-sensitive", while 68.8% of area postrema neurons responding to vasopressin with increases in firing frequency were classified as "blood pressure-sensitive". In contrast, 78.6% of nucleus tractus solitarius neurons that decreased firing frequency in response to vasopressin and 55.5% of those that increased firing frequency were classified as "blood pressure-sensitive" neurons. To determine whether the actions of vasopressin in the area postrema were mediated by V1 receptors the effect of vasopressin after V1 receptor blockade was examined in seven "vasopressin-sensitive" area postrema neurons. All seven neurons tested showed no response to vasopressin after such V1 receptor blockade. These data suggest that there exists a population of area postrema neurons specifically responsive to circulating vasopressin as a result of actions of this peptide at V1 receptors. They also implicate these neurons in the physiological mechanisms through which circulating vasopressin acts in the area postrema to influence baroreceptor reflex sensitivity.

Animals↗

PubMed1994

Cardiovascular and single-unit responses to subfornical organ stimulation are abolished by pentobarbital anesthesia.

The nature of reflex cardiovascular responses to electrical stimulation in the central nervous system has been suggested to be influenced by anesthetic. We report here that pressor responses to subfornical organ stimulation observed in urethane-anesthetized rats (n = 4) are absent, or reversed in animals under pentobarbital anesthesia (n = 5; Student's t test, p < 0.01, compared with urethane anesthesia. Single-unit recordings from identified hypothalamic neurons (n = 60) showed that the activation of these cells, by subfornical organ efferents, with systemic angiotensin observed in urethane-anesthetized animals (29 of 39 cells tested), was not observed under pentobarbital anesthesia (2 of 21 cells tested). Bicuculline treatment of pentobarbital-anesthetized rats (n = 5) restores small pressor responses to subfornical organ stimulation (t test, p < 0.05), suggesting that potentiated GABA inhibition underlies this modified state under pentobarbital anesthesia.

Angiotensin II↗

PubMed1994

Autonomic pathways in development of neural stimulation-induced gastric mucosal damage.

Gastric mucosal erosions can be induced by electrical stimulation of either vagus nerves (5 Hz, 5 V, 1 ms) or the paraventricular nucleus (PVN) of the hypothalamus (200 microA, 60 Hz, 100-microseconds pulse width). We have utilized various pharmacological and surgical interventions to determine the contributions of different components of the autonomic nervous system to the development of this neurally induced gastric damage in urethan-anesthetized Sprague-Dawley rats. In all experiments damage was assessed macroscopically and scored blindly on a 0 (normal) to 3 (severe) scale with samples sectioned for subsequent histological assessment of damage at the light microscopic level. Animals pretreated with either hexamethonium (30 mg/kg iv) or atropine (2 mg/kg iv) demonstrated reduced gastric damage scores after vagal stimulation compared with untreated control animals (P < 0.05). In contrast animals that underwent cervical cord transection exhibited gastric damage after both vagal and PVN stimulation that was not significantly different compared with animals with an intact cord undergoing similar stimulation (P > 0.05). Such cord transection itself did not cause any significant change to the gastric mucosa in the time period studied. These data emphasize the importance of the autonomic nervous system, in particular the parasympathetic component in the development of vagal stimulation-induced gastric damage. In addition, the present studies suggest that neither vagal nor PVN stimulation-induced gastric damage is dependent on neural projections to sympathetic preganglionic neurons of the intermediolateral cell column of the spinal cord.

Animals↗

PubMed1994

Nitric oxide actions in paraventricular nucleus: cardiovascular and neurochemical implications.

We have examined potential functions of nitric oxide (NO) within the paraventricular nucleus (PVN) in urethan-anesthetized male Sprague-Dawley rats. Initial experiments demonstrated microinjection of 50 pmol of the NO donor, sodium nitroprusside (SNP), directly into the PVN resulted in significant decreases in mean blood pressure (BP) (-3,312 +/- 1,189 mmHg/s over 300-s response time; P < 0.05). To determine whether such effects were attributable to SNP-induced NO release, NO was administered into PVN directly by bilateral microdialysis of NO-containing artificial cerebrospinal fluid (NO-aCSF), a process that results in delivery of approximately 50 pmol NO.PVN-1 x min-1. Such microdialysis resulted in significant decreases in BP (-5,121 +/- 817 mmHg/s over 1,200-s response time; P < 0.005), while aCSF microdialysis was without effect (1,298 +/- 1,071 mmHg/s over 1,200-s response time; P > 0.1). Amino acid concentrations were measured in dialysates collected during perfusion of the same PVN sites with either aCSF or NO-aCSF by high-performance liquid chromatography (HPLC) analysis. NO-aCSF induced significant increases in aspartate (aCSF 31 +/- 7 pmol/30 min; NO-aCSF 134 +/- 33 pmol/30 min; P < 0.05), glutamate (aCSF 36 +/- 5 pmol/30 min; NO-aCSF 417 +/- 108 pmol/30 min; P < 0.02), gamma-aminobutyric acid (aCSF 4.1 +/- 0.7 pmol/30 min; NO-aCSF 104 +/- 29 pmol/30 min; P < 0.02), and taurine (aCSF 34 +/- 3 pmol/30 min; NO-aCSF 117 +/- 24 pmol/30 min; P < 0.01) concentrations, while alanine, glutamine, and serine concentrations were unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

PubMed1993

Angiotensin II responsiveness of rat paraventricular and subfornical organ neurons in vitro.

The responsiveness of neurons in the hypothalamic paraventricular nucleus to angiotensin II was investigated using extracellular single unit recording techniques in rat brain slices. Bath application of angiotensin II at a concentration of 3 x 10(-7) M for 2-5 min resulted in excitatory responses in 50.4% of 141 paraventricular cells tested. The mean increase in firing rate was 2.12 +/- 0.20 (mean +/- S.E.M.) spikes/s, which represents a mean increase in activity of 149.8 +/- 16.5%. Angiotensin II-sensitive neurons usually displayed irregular, phasic, or very slow spontaneous activity, with the majority of these neurons located in the magnocellular region. Under physiological blockade of synaptic transmission with low Ca2+/high Mg2+ medium, neuronal responses to this peptide remained in 12 (92.3%) of 13 cells tested. Application of three successive doses of angiotensin II ranging from 3 x 10(-9)-3 x 10(-7) M showed that neuronal responses were dose-dependent with an estimated threshold of 10(-8) M. In comparison with angiotensin III, angiotensin II not only stimulated more paraventricular cells, but usually induced larger excitatory responses. Angiotensin II subtype 1 receptor antagonist losartan completely blocked angiotensin II responsiveness in each of 14 paraventricular cells tested whereas PD 123319, an angiotensin II subtype 2 receptor antagonist, exhibited a partial inhibitory effect in about one half of another 13 cells. In addition, single unit in vitro subfornical organ recordings demonstrate that angiotensin II evokes greater excitatory responses than in the paraventricular nucleus and that these effects are abolished by losartan application. These results support the hypothesis that within both the paraventricular nucleus and subfornical organ angiotensin II is a bioactive peptide which modulates neuronal activity and thus may exert significant control over neuroendocrine and autonomic functions.

Action Potentials↗

PubMed1993

Functional evidence that the angiotensin antagonist losartan crosses the blood-brain barrier in the rat.

Losartan is a novel nonpeptidergic antagonist of angiotensin (ANG) II subtype 1 (AT1) receptors, which effectively lowers blood pressure in high-renin hypertensive rat and blocks the pressor response to systemic ANG II. It is well known that high densities of ANG II receptors exist in the hypothalamic paraventricular nucleus (PVN). In addition, activation of putative angiotensinergic afferents to the PVN originating in subfornical organ (SFO) elevates blood pressure and facilitates the activity of PVN neurons. We report here that systemic administration of losartan (3 mg/kg) significantly attenuates the pressor response to electrical stimulation of SFO. The excitatory responses of PVN neurons to SFO stimulation or local pressure microinjection of ANG II were also significantly inhibited in 58.8% and 88.9% of PVN cells, respectively, by intravenous administration of losartan. These pharmacological effects were rapid and reversible, and were accompanied by little change of basal arterial blood pressure or spontaneous neuronal activity. These observations suggest that systemic losartan crosses the blood-brain barrier (BBB) and acts at AT1 receptors within the PVN.

Afferent Pathways↗

PubMed1993

Subfornical organ efferents to paraventricular nucleus utilize angiotensin as a neurotransmitter.

In this study, we have utilized electrophysiological single unit recordings to evaluate the effects of nonpeptidergic angiotensin II (ANG II) antagonists on neural responses of hypothalamic paraventricular nucleus (PVN) neurons to either electrical stimulation in subfornical organ (SFO) or direct application of ANG II. Electrical stimulation (200-400 microA; 0.1 ms) in the SFO resulted in excitatory responses in 36 of 50 PVN neurons tested. Peristimulus histogram analysis of such excitatory effects demonstrated latencies of < 30 ms and variability of response times of approximately 50 ms in 14 of these 36 neurons. In view of previous anatomic and electrophysiological studies such inputs were therefore considered to be monosynaptically mediated by direct neural inputs from the SFO. The remaining 22 cells excited by such SFO stimulation showed responses of longer latency and duration suggestive of a different underlying synaptic mechanism. Local pressure ejection of ANG II into the PVN resulted in increased neural activity in 50% (9 of 18) of the neurons tested. After systemic (3 mg/kg iv) or local (2 x 10(-2) M; 1-25 s; 2-40 psi) microinjection of the nonpeptidergic angiotensin II1 (AT1) receptor antagonist losartan, SFO excitations were attenuated in 63.9% (23 of 36) of the PVN neurons tested, such pharmacologically blocked excitatory responses being reduced by 68.3 +/- 5.2% from control stimulation effects (P < 0.001). Similar losartan-induced attenuations of both short latency (presumed monosynaptic) (50.0%) and longer latency (72.7%) responses were observed. In addition, losartan also abolished the excitatory effects of local administration of ANG II on 77.8% (7 of 9) of ANG II-sensitive neurons in PVN tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗