Subfornical organ efferents to paraventricular nucleus utilize angiotensin as a neurotransmitter

1993 ◽  
Vol 265 (2) ◽  
pp. R302-R309 ◽  
Author(s):  
Z. Li ◽  
A. V. Ferguson
Keyword(s):  
Electrical Stimulation ◽  
Paraventricular Nucleus ◽  
Response Times ◽  
Subfornical Organ ◽  
Ang Ii ◽  
Neural Responses ◽  
Local Pressure ◽  
Electrophysiological Studies ◽  
Excitatory Responses ◽  
Control Stimulation

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)

Water deprivation upregulates ANG II AT1 binding and mRNA in rat subfornical organ and anterior pituitary

1997 ◽  
Vol 273 (1) ◽  
pp. E156-E163 ◽  
Author(s):  
G. L. Sanvitto ◽  
O. Johren ◽  
W. Hauser ◽  
J. M. Saavedra
Keyword(s):  
Paraventricular Nucleus ◽  
Median Eminence ◽  
Anterior Pituitary ◽  
Water Deprivation ◽  
Subfornical Organ ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Ang Ii ◽  
At1 Receptors ◽  
Receptor Mrna

We studied angiotensin II (ANG II) receptor subtype expression in selected brain nuclei and pituitary gland after water deprivation by in vitro receptor autoradiography using 125I-labeled [Sar1]ANG II and by in situ hybridization using 35S-labeled AT1A, AT1B, and AT2 receptor-specific riboprobes. In control rats we found binding to AT1 receptors in the subfornical organ, paraventricular nucleus, median eminence, and anterior pituitary; AT1A mRNA expression in the subfornical organ and paraventricular nucleus; and AT1B mRNA expression in the anterior pituitary. No receptor mRNA was found in the median eminence. AT1 receptors and AT1A receptor mRNA levels were increased in the subfornical organ, and, in the anterior pituitary, AT1 receptors and AT1B receptor mRNA were increased, only after 5 days of water deprivation. No significant changes occurred after 1 or 3 days of water deprivation, and no regulation of ANG II receptor expression was detected in other brain areas. Our results show that prolonged water deprivation selectively regulates AT1 receptor expression and AT1A and AT1B receptor mRNA levels in the subfornical organ and anterior pituitary, respectively, supporting a role for these receptors during sustained dehydration.

ANG II in the paraventricular nucleus potentiates the cardiac sympathetic afferent reflex in rats with heart failure

2004 ◽  
Vol 97 (5) ◽  
pp. 1746-1754 ◽  
Author(s):  
Guo-Qing Zhu ◽  
Lie Gao ◽  
Kuashik P. Patel ◽  
Irving H. Zucker ◽  
Wei Wang
Keyword(s):  
Heart Failure ◽  
Electrical Stimulation ◽  
Paraventricular Nucleus ◽  
Sham Group ◽  
Ang Ii ◽  
Renal Sympathetic Nerve Activity ◽  
Afferent Nerves ◽  
Coronary Ligation ◽  
Cardiac Sympathetic Afferent Reflex ◽  
Renal Sympathetic

Chronic heart failure (CHF) is characterized by sympathoexcitation, and the cardiac sympathetic afferent reflex (CSAR) is a sympathoexcitatory reflex. Our previous studies have shown that the CSAR was enhanced in CHF. In addition, central angiotensin II (ANG II) is an important modulator of this reflex. This study was performed to determine whether the CSAR evoked by stimulation of cardiac sympathetic afferent nerves (CSAN) in rats with coronary ligation-induced CHF is enhanced by ANG II in the paraventricular nucleus (PVN). Under α-chloralose and urethane anesthesia, renal sympathetic nerve activity (RSNA) was recorded. The RSNA responses to electrical stimulation (5, 10, 20, and 30 Hz) of the CSAN were evaluated. Bilateral microinjection of the AT1-receptor antagonist losartan (50 nmol) into the PVN had no significant effects in the sham group, but it abolished the enhanced RSNA response to stimulation in the CHF group. Unilateral microinjection of three doses of ANG II (0.03, 0.3, and 3 nmol) into the PVN resulted in dose-related increases in the RSNA responses to stimulation. Although ANG II also potentiated the RSNA response to electrical stimulation in sham rats, the RSNA responses to stimulation after ANG II into the PVN in rats with CHF were much greater than in sham rats. The effects of ANG II were prevented by pretreatment with losartan into the PVN in CHF rats. These results suggest that the central gain of the CSAR is enhanced in rats with coronary ligation-induced CHF and that ANG II in the PVN augments the CSAR evoked by CSAN, which is mediated by the central angiotensin AT1 receptors in rats with CHF.

Effect of paraventricular nucleus lesions on cardiovascular responses elicited by stimulation of the subfornical organ in the rat

1985 ◽  
Vol 63 (7) ◽  
pp. 816-824 ◽  
Author(s):  
Michael B. Gutman ◽  
John Ciriello ◽  
Gordon J. Mogenson
Keyword(s):  
Electrical Stimulation ◽  
Arterial Pressure ◽  
Paraventricular Nucleus ◽  
Pressor Response ◽  
Cardiovascular Responses ◽  
Subfornical Organ ◽  
Short Latency ◽  
Peak Latency ◽  
Ganglionic Blockade ◽  
Stimulation Of

It has recently been reported that stimulation of the region of the subfornical organ (SFO) elicits an increase in arterial pressure. However, the mechanisms and forebrain neural circuitry that are involved in this cardiovascular response have not been elucidated. The present study was done in urethane-anaesthetized rats to determine whether selective activation of SFO neurons elicit cardiovascular responses and whether these responses were mediated by a pathway involving the paraventricular nucleus of the hypothalamus (PVH). Stimulation sites which required the lowest threshold current (30 μA) to elicit a pressor response and at which the largest rise in mean arterial pressure (MAP; 22 ± 2 mmHg) was elicited at a constant current intensity (150 μA) were histologically localized in the region of the SFO. Short (mean peak latency; 4 ± 2 s) and long (mean peak latency; 61 ± 8 s) latency increases in MAP were observed during and after electrical stimulation of the SFO, respectively. Cardiac slowing accompanied the short latency pressor response and cardioacceleration was observed in most (57%) of the cases to accompany the late pressor response. Microinjection of L-glutamate into the SFO consistently elicited cardiovascular responses qualitatively similar to those observed during electrical stimulation. Ganglionic blockade abolished the short latency increase in MAP and the accompanying bradycardia. However, the long latency pressor and cardioacceleratory responses were not altered by ganglionic blockade and adrenalectomy. Selective bilateral electrolytic or kainic acid lesions of the region of the PVH significantly attenuated the cardiovascular responses elicited by stimulation of the SFO. These data suggest that activation of neurons in the SFO elicit cardiovascular responses partially mediated by sympathetic outflow through a neural pathway involving the PVH.

Multiple receptor subtypes mediate the effects of serotonin on rat subfornical organ neurons

1998 ◽  
Vol 275 (6) ◽  
pp. R2035-R2042 ◽  
Author(s):  
Karie E. Scrogin ◽  
Alan Kim Johnson ◽  
Herbert A. Schmid
Keyword(s):  
Receptor Agonist ◽  
Brain Slice ◽  
Subfornical Organ ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
Excitatory Responses ◽  
Rat Brain Slice ◽  
Dose Dependent ◽  
Multiple Receptor ◽  
Serotonergic Innervation

The subfornical organ (SFO) receives significant serotonergic innervation. However, few reports have examined the functional effects of serotonin on SFO neurons. This study characterized the effects of serotonin on spontaneously firing SFO neurons in the rat brain slice. Of 31 neurons tested, 80% responded to serotonin (1–100 μM) with either an increase ( n = 15) or decrease ( n = 10) in spontaneous activity. Responses to serotonin were dose dependent and persisted after synaptic blockade. Excitatory responses could also be mimicked by the 5-hydroxytryptamine (5-HT)2A/2C receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI; 1–10 μM) and could be blocked by the 5-HT2A/2C-receptor antagonist LY-53,857 (10 μM). LY-53,857 unmasked inhibitory responses to serotonin in 56% of serotonin-excited cells tested. Serotonin-inhibited cells were also inhibited by the 5-HT1A-receptor agonist 8-hydroxy-2(di- n-propylamino)tetralin (8-OH-DPAT; 1–10 μM; n = 7). The data indicate that SFO neurons are responsive to serotonin via postsynaptic activation of multiple receptor subtypes. The results suggest that excitatory responses to serotonin are mediated by 5-HT2A or 5-HT2C receptors and that inhibitory responses may be mediated by 5-HT1A receptors. In addition, similar percentages of serotonin-excited and -inhibited cells were also sensitive to ANG II. As such the functional relationship between serotonin and ANG II in the SFO remains unclear.

Functional identification of central pressor pathways originating in the subfornical organ

1991 ◽  
Vol 69 (7) ◽  
pp. 1035-1045 ◽  
Author(s):  
John Ciriello ◽  
Michael B. Gutman
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
Paraventricular Nucleus ◽  
Supraoptic Nucleus ◽  
Subfornical Organ ◽  
Preoptic Nucleus ◽  
Thoracic Spinal Cord ◽  
Median Preoptic Nucleus ◽  
Pressor Responses ◽  
Stimulation Of

The functional projections from pressor sites in the subfornical organ (SFO) were identified using the 2-deoxyglucose (2-DG) autoradiographic method in urethane-anesthetized, sinoaortic-denervated rats. Autoradiographs of brain and spinal cord sections taken from rats whose SFO was continuously stimulated electrically for 45 min with stereotaxically placed monopolar electrodes (150 μA, 1.5-ms pulse duration, 15 Hz) following injection of tritiated 2-DG were compared with control rats that received intravenous infusions of pressor doses of phenylephrine to mimic the increase in arterial pressure observed during SFO stimulation. Comparisons were also made to autoradiographs from rats in which the ventral fornical commissure (CFV), just dorsal to the SFO, was electrically stimulated. The pressor responses during either electrical stimulation of the SFO or intravenous infusion of phenylephrine were similar in magnitude. On the other hand, stimulation of the CFV did not elicit a significant pressor response. Electrical stimulation of the SFO increased 2-DG uptake, in comparison to the phenylephrine-infused rats, in the nucleus triangularis, septofimbrial nucleus, lateral septal nucleus, nucleus accumbens, bed nucleus of the stria terminalis, dorsal and ventral nucleus medianus (median preoptic nucleus), paraventricular nucleus of the thalamus, hippocampus, supraoptic nucleus, suprachiasmatic nucleus, paraventricular nucleus of the hypothalamus, and the intermediolateral nucleus of and central autonomic area of the thoracic spinal cord. In contrast, in rats whose CFV was stimulated, these nuclei did not demonstrate changes in 2-DG uptake compared with control animals that received pressor doses of phenylephrine. These data have demonstrated some of the components of the neural circuitry likely involved in mediating the pressor responses to stimulation of the SFO and the corrective responses to activation of the SFO by disturbances to circulatory and fluid balance homeostasis.Key words: cardiovascular reflex pathways, drinking, median preoptic nucleus, osmoreceptors, paraventricular nucleus of the hypothalamus, supraoptic nucleus.

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

1992 ◽  
Vol 70 (5) ◽  
pp. 779-785 ◽  
Author(s):  
Alastair V. Ferguson ◽  
Katharine M. Wall
Keyword(s):  
Blood Pressure ◽  
Area Postrema ◽  
Circumventricular Organs ◽  
Subfornical Organ ◽  
Cardiovascular Control ◽  
Multiple Roles ◽  
Ang Ii ◽  
Electrophysiological Studies ◽  
The Central Nervous System ◽  
Central Actions

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.Key words: blood pressure regulation, circumventricular organs, vasopressin, area postrema, subfornical organ.

Systemic angiotensin acts at subfornical organ to facilitate activity of neurohypophysial neurons

1986 ◽  
Vol 251 (4) ◽  
pp. R712-R717 ◽  
Author(s):  
A. V. Ferguson ◽  
L. P. Renaud
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Electrical Stimulation ◽  
Subfornical Organ ◽  
System Structure ◽  
Ang Ii ◽  
Cell Excitability ◽  
Long Duration ◽  
The Central Nervous System ◽  
Synaptic Changes

Extracellular single unit recordings were obtained to investigate the effects of systemic administration of angiotensin II (ANG II) on the excitability of antidromically identified neurohypophysial neurons in the rat. Records were obtained from 89 oxytocin- or vasopressin-secreting neurons in the hypothalamic supraoptic or paraventricular nuclei. Increased excitability in response to ANG II was observed in 83% of putative vasopressin- and 75% of putative oxytocin-secreting neurons tested in intact animals. Lesion studies to identify the central nervous system site of action for such peripherally administered ANG II showed that, after electrolytic lesion of the rostral subfornical organ (SFO), neurohypophysial neurons demonstrated no increase in excitability in response to this peptide. In an attempt to correlate the synaptic events through which activation of SFO neurons may result in facilitated excitability of neurohypophysial cells, 19 cells were tested with both systemic ANG II and electrical stimulation in the SFO. These studies demonstrated that all cells which showed long-duration increases in excitability in response to electrical stimulation of SFO were also activated by systemic ANG II. It is concluded that the SFO is an essential central nervous system structure in eliciting increases in the excitability of both oxytocin- and vasopressin-secreting neurons in response to systemic ANG II. These effects may involve the activation of SFO efferents that evoke long-duration post-synaptic changes in neurohypophysial cell excitability.

Microinjection of ANG II into paraventricular nucleus enhances cardiac sympathetic afferent reflex in rats

2002 ◽  
Vol 282 (6) ◽  
pp. H2039-H2045 ◽  
Author(s):  
Guo-Qing Zhu ◽  
Kuashik P. Patel ◽  
Irving H. Zucker ◽  
Wei Wang
Keyword(s):  
Electrical Stimulation ◽  
Paraventricular Nucleus ◽  
Sympathetic Nerve Activity ◽  
Sympathetic Nerves ◽  
Ang Ii ◽  
Renal Sympathetic Nerve Activity ◽  
Afferent Nerves ◽  
Cardiac Sympathetic Afferent Reflex ◽  
Renal Sympathetic

The aims of present study were to determine whether angiotensin II (ANG II) in the paraventricular nucleus (PVN) is involved in the central integration of the cardiac sympathetic afferent reflex and whether this effect is mediated by the ANG type 1 (AT1) receptor. While the animals were under α-chloralose and urethane anesthesia, mean arterial pressure, heart rate, and renal sympathetic nerve activity (RSNA) were recorded in sinoaortic-denervated and cervical-vagotomized rats. A cannula was inserted into the left PVN for microinjection of ANG II. The cardiac sympathetic afferent reflex was tested by electrical stimulation (5, 10, 20, and 30 Hz in 10 V and 1 ms) of the afferent cardiac sympathetic nerves or epicardial application of bradykinin (BK) (0.04 and 0.4 μg in 2 μl). Microinjection of ANG II (0.03, 0.3, and 3 nmol) into the PVN resulted in dose-related increases in the RSNA responses to electrical stimulation. The percent change of RSNA response to 20- and 30-Hz stimulation increased significantly at the highest dose of ANG II (3 nmol). The effects of ANG II were prevented by pretreatment with losartan (50 nmol) into the PVN. Microinjection of ANG II (0.3 nmol) into the PVN significantly enhanced the RSNA responses to epicardial application of BK, which was abolished by pretreatment with losartan (50 nmol) into the PVN. These results suggest that exogenous ANG II in the PVN augments the cardiac sympathetic afferent reflex evoked by both electrical stimulation of cardiac sympathetic afferent nerves and epicardial application of BK. These central effects of ANG II are mediated by AT1 receptors.

scholarly journals Median preoptic nucleus and subfornical organ drive renal sympathetic nerve activity via a glutamatergic mechanism within the paraventricular nucleus

2012 ◽  
Vol 302 (4) ◽  
pp. R424-R432 ◽  
Author(s):  
Tamra Llewellyn ◽  
Hong Zheng ◽  
Xuefei Liu ◽  
Bo Xu ◽  
Kaushik P. Patel
Keyword(s):  
Paraventricular Nucleus ◽  
Neural Control ◽  
Extracellular Recording ◽  
Subfornical Organ ◽  
Receptor Blocker ◽  
Ang Ii ◽  
Preoptic Nucleus ◽  
Median Preoptic Nucleus ◽  
Renal Sympathetic

The paraventricular nucleus (PVN) of the hypothalamus is involved in the neural control of sympathetic drive, but the precise mechanism(s) that influences the PVN is not known. The activation of the PVN may be influenced by input from higher forebrain areas, such as the median preoptic nucleus (MnPO) and the subfornical organ (SFO). We hypothesized that activation of the MnPO or SFO would drive the PVN through a glutamatergic pathway. Neuroanatomical connections were confirmed by the recovery of a retrograde tracer in the MnPO and SFO that was injected bilaterally into the PVN in rats. Microinjection of 200 pmol of N-methyl-d-aspartate (NMDA) or bicuculline-induced activation of the MnPO and increased renal sympathetic activity (RSNA), mean arterial pressure, and heart rate in anesthetized rats. These responses were attenuated by prior microinjection of a glutamate receptor blocker AP5 (4 nmol) into the PVN (NMDA − ΔRSNA 72 ± 8% vs. 5 ± 1%; P < 0.05). Using single-unit extracellular recording, we examined the effect of NMDA microinjection (200 pmol) into the MnPO on the firing activity of PVN neurons. Of the 11 active neurons in the PVN, 6 neurons were excited by 95 ± 17% ( P < 0.05), 1 was inhibited by 57%, and 4 did not respond. The increased RSNA after activation of the SFO by ANG II (1 nmol) or bicuculline (200 pmol) was also reduced by AP5 in the PVN (for ANG II − ΔRSNA 46 ± 7% vs. 17 ± 4%; P < 0.05). Prior microinjection of ANG II type 1 receptor blocker losartan (4 nmol) into the PVN did not change the response to ANG II or bicuculline microinjection into the SFO. The results from this study demonstrate that the sympathoexcitation mediated by a glutamatergic mechanism in the PVN is partially driven by the activation of the MnPO or SFO.

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