Endogenous angiotensin II facilitates GABAergic neurotransmission afferent to the Na+-responsive neurons of the rat median preoptic nucleus

2009 ◽  
Vol 297 (3) ◽  
pp. R783-R792 ◽  
Author(s):  
Mélaine Henry ◽  
Magali Grob ◽  
Didier Mouginot
Keyword(s):  
Reversal Potential ◽  
Gaba Release ◽  
Serum Levels ◽  
Inhibitory Response ◽  
Ang Ii ◽  
Preoptic Nucleus ◽  
Gabaergic Neurotransmission ◽  
Median Preoptic Nucleus ◽  
Neuronal Populations ◽  
Efferent Projections

The median preoptic nucleus (MnPO) is densely innervated by efferent projections from the subfornical organ (SFO) and, therefore, is an important relay for the peripheral chemosensory and humoral information (osmolality and serum levels ANG II). In this context, controlling the excitability of MnPO neuronal populations is a major determinant of body fluid homeostasis and cardiovascular regulation. Using a brain slice preparation and patch-clamp recordings, our study sought to determine whether endogenous ANG II modulates the strength of the SFO-derived GABAergic inputs to the MnPO. Our results showed that the amplitude of the inhibitory postsynaptic currents (IPSCs) were progressively reduced by 44 ± 2.3% by (Sar1, Ile8)-ANG II, a competitive ANG type 1 receptor (AT1R) antagonist. Similarly, losartan, a nonpeptidergic AT1R antagonist decreased the IPSC amplitude by 40.4 ± 5.6%. The facilitating effect of endogenous ANG II on the GABAergic input to the MnPO was not attributed to a change in GABA release probability and was mimicked by exogenous ANG II, which potentiated the amplitude of the muscimol-activated GABAA/Cl− current by 53.1 ± 11.4%. These results demonstrate a postsynaptic locus of action of ANG II. Further analysis reveals that ANG II did not affect the reversal potential of the synaptic inhibitory response, thus privileging a cross talk between postsynaptic AT1 and GABAA receptors. Interestingly, facilitation of GABAergic neurotransmission by endogenous ANG II was specific to neurons responding to changes in the ambient Na+ level. This finding, combined with the ANG II-mediated depolarization of non-Na+-responsive neurons reveals the dual actions of ANG II to modulate the excitability of MnPO neurons.

Angiotensin II Induces Calcium-Dependent Rhythmic Activity in a Subpopulation of Rat Hypothalamic Median Preoptic Nucleus Neurons

2005 ◽  
Vol 93 (4) ◽  
pp. 1970-1976 ◽  
Author(s):  
David Spanswick ◽  
Leo P. Renaud
Keyword(s):  
Angiotensin Ii ◽  
Reversal Potential ◽  
Rhythmic Activity ◽  
Input Resistance ◽  
Resting Membrane Potential ◽  
Ang Ii ◽  
Preoptic Nucleus ◽  
Bathing Medium ◽  
Membrane Hyperpolarization ◽  
Median Preoptic Nucleus

Whole cell patch-clamp recordings revealed a subpopulation (16%, n = 18/112) of rat median preoptic nucleus (MnPO) neurons responded to bath-applied angiotensin II (Ang II; 100 nM to 5 μM; 30–90 s) with a prolonged TTX-resistant membrane depolarization and rhythmic bursting activity. At rest, cells characteristically displayed relatively low input resistance and negative resting potentials. Ang-II-induced responses featured increased input resistance, a reversal potential of −95 ± 2 mV, an increase in action potential duration from 2.9 ± 0.5 to 4.3 ± 0.8 ms, and the appearance of a rebound excitation at the offset of membrane responses to hyperpolarizing current injection. The latter was sensitive to Ni2+ (0.5–1 mM; n = 5), insensitive to extracellular Cs+ (1 mM, n = 7), and intracellular QX-314 (4 mM, n = 5), consistent with activation of a T-type Ca2+ conductance. Coincident with the Ang-II-induced depolarization was the appearance of rhythmic depolarizing shifts at a frequency of 0.14 ± 0.09 Hz with superimposed bursts of 4–22 action potentials interspersed with silent periods persisting for >1 h after washout. These TTX-resistant depolarizing shifts increased in amplitude and decreased in frequency with membrane hyperpolarization with activity ceasing beyond approximately –80mV, and were abolished in low-Ca2+/high-Mg2+ bathing medium ( n = 6), Co2+ (1 mM; n = 6), or Ni2+ (0.5–1 mM; n = 8). Thus in a subpopulation of MnPO neurons, Ang II induces “pacemaker-like” activity by reducing a K+-dependent leak conductance that contributes to resting membrane potential and promoting of Ca2+-dependent regenerative auto-excitation mediated, in part, by a T-type Ca2+ conductance.

Neuronal Sodium Leak Channel Is Responsible for the Detection of Sodium in the Rat Median Preoptic Nucleus

2011 ◽  
Vol 105 (2) ◽  
pp. 650-660 ◽  
Author(s):  
Christina Tremblay ◽  
Emmanuelle Berret ◽  
Mélaine Henry ◽  
Benjamin Nehmé ◽  
Louis Nadeau ◽  
...  
Keyword(s):  
Close Contact ◽  
Critical Role ◽  
Reversal Potential ◽  
Outward Current ◽  
The Body ◽  
Equilibrium Potential ◽  
Preoptic Nucleus ◽  
Leak Channel ◽  
Median Preoptic Nucleus ◽  
Electrophysiological Recordings

Sodium (Na+) ions are of primary importance for hydromineral and cardiovascular homeostasis, and the level of Na+ in the body fluid compartments [plasma and cerebrospinal fluid (CSF)] is precisely monitored in the hypothalamus. Glial cells seem to play a critical role in the mechanism of Na+ detection. However, the precise role of neurons in the detection of extracellular Na+ concentration ([Na+]out) remains unclear. Here we demonstrate that neurons of the median preoptic nucleus (MnPO), a structure in close contact with the CSF, are specific Na+ sensors. Electrophysiological recordings were performed on dissociated rat MnPO neurons under isotonic [Na+] (100 mM NaCl) with local application of hypernatriuric (150, 180 mM NaCl) or hyponatriuric (50 mM NaCl) external solution. The hyper- and hyponatriuric conditions triggered an in- and an outward current, respectively. The reversal potential of the current matched the equilibrium potential of Na+, indicating that a change in [Na+]out modified the influx of Na+ in the MnPO neurons. The conductance of the Na+ current was not affected by either the membrane potential or the [Na+]out. Moreover, the channel was highly selective for lithium over guanidinium. Together, these data identified the channel as a Na+ leak channel. A high correlation between the electrophysiological recordings and immunofluorescent labeling for the NaX channel in dissociated MnPO neurons strongly supports this channel as a candidate for the Na+ leak channel responsible for the Na+-sensing ability of rat MnPO neurons. The absence of NaX labeling and of a specific current evoked by a change in [Na+]out in mouse MnPO neurons suggests species specificity in the hypothalamus structures participating in central Na+ detection.

Central angiotensin induction of fetal brain c-fos expression and swallowing activity

2001 ◽  
Vol 280 (6) ◽  
pp. R1837-R1843 ◽  
Author(s):  
Zhice Xu ◽  
Calvario Glenda ◽  
Linda Day ◽  
Jiaming Yao ◽  
Michael G. Ross
Keyword(s):  
Body Fluid ◽  
Drinking Behavior ◽  
Fetal Brain ◽  
Cellular Responses ◽  
Ang Ii ◽  
Preoptic Nucleus ◽  
Median Preoptic Nucleus ◽  
Fluid Regulation ◽  
Fos Expression ◽  
Near Term

The present study examined physiological and cellular responses to central application of ANG II in ovine fetuses and determined the fetal central ANG-mediated dipsogenic sites in utero. Chronically prepared near-term ovine fetuses (130 ± 2 days) received injection of ANG II (1.5 μg/kg icv). Fetuses were monitored for 3.5 h for swallowing activity, after which animals were killed and fetal brains were perfused for subsequent Fos staining. Intracerebroventricular ANG II significantly increased fetal swallowing in near-term ovine fetuses (1.1 ± 0.2 to 4.5 ± 1.0 swallows/min). The initiation of stimulated fetal swallowing activity was similar to the latency of thirst responses (drinking behavior) elicited by central ANG II in adult animals. ANG II evoked increased Fos staining in putative dipsogenic centers, including the subfornical organ, organum vasculosum of the lamina terminalis, and median preoptic nucleus. Intracerebroventricular injection of ANG II also caused c- fos expression in the fetal hindbrain. These results indicate that an ANG II-mediated central dipsogenic mechanism is intact before birth, acting at sites consistent with the dipsogenic neural network. Central ANG II mechanisms likely contribute to fetal body fluid and amniotic fluid regulation.

Median preoptic nucleus ablation does not affect angiotensin II-induced hypertension

1986 ◽  
Vol 251 (1) ◽  
pp. H148-H152
Author(s):  
G. D. Fink ◽  
C. A. Bruner ◽  
M. L. Mangiapane
Keyword(s):  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Cardiovascular Responses ◽  
Base Line ◽  
Ang Ii ◽  
Preoptic Nucleus ◽  
Water Excretion ◽  
Median Preoptic Nucleus ◽  
Induced Hypertension

Previous studies implicated the ventral median preoptic nucleus (MNPOv) in cardiovascular responses to circulating and intracerebroventricular angiotensin II (ANG II) and in normal cardiovascular and fluid homoeostasis. In the present experiments, chronically catheterized rats received continuous (24 h/day) intravenous infusions of ANG II (10 ng/min) for 5 days, and changes in mean arterial pressure, heart rate, water intake and urinary electrolyte and water excretion were determined daily. Three groups of rats were compared as follows: 1) sham-operated control rats (n = 12), 2) rats with 20-70% of the MNPOv ablated electrolytically (n = 6), and 3) rats with over 90% of the MNPOv ablated (n = 5). The organum vasculosum of the lamina terminalis was intact in all three groups. Base-line values of all measured variables were identical in the three groups on two control days preceding ANG II infusion and on two recovery days after infusion. During the administration of ANG II for 5 days, mean arterial pressure rose significantly (and similarly) in all three groups of rats; no other variable was significantly affected by ANG II infusion. These results suggest that neural pathways originating in, or passing through, the MNPOv region are not critical in the pathogenesis of ANG II-induced hypertension in the rat.

Increased angiotensin II receptors in brain nuclei of DOCA-salt hypertensive rats

1988 ◽  
Vol 255 (3) ◽  
pp. H646-H650 ◽  
Author(s):  
J. S. Gutkind ◽  
M. Kurihara ◽  
J. M. Saavedra
Keyword(s):  
Angiotensin Ii ◽  
Area Postrema ◽  
Experimental Hypertension ◽  
Ang Ii ◽  
Preoptic Nucleus ◽  
Salt Treatment ◽  
Brain Nuclei ◽  
Median Preoptic Nucleus ◽  
Wistar Kyoto

We analyzed angiotensin II (ANG II) receptors by in vitro autoradiography in selective brain nuclei of control, salt-treated (1% NaCl in drinking water), deoxycorticosterone acetate (DOCA)-treated (DOCA pivalate, 25 mg/kg sc weekly), and DOCA-salt-treated (DOCA + salt treatments) uninephrectomized male Wistar-Kyoto rats. After 4 wk of treatment, only the DOCA-salt group developed hypertension. ANG II binding increased in median preoptic nucleus and subfornical organ of salt- and DOCA-treated rats. DOCA-treated rats also showed increased ANG II binding in paraventricular nucleus. DOCA-salt-treated rats showed higher ANG II binding in nucleus of the solitary tract and area postrema, as well as in the areas mentioned before. Although salt and/or DOCA treatments alone increased ANG II receptors in some brain nuclei, after combined DOCA-salt treatment there was significantly higher ANG II binding in all areas, except the median preoptic nucleus. These results suggest that increased ANG II receptors in selected brain areas may play a role in the pathophysiology of mineralocorticoid-salt experimental hypertension.

Comparison of fos-like immunoreactivity induced in rat brain by central injection of angiotensin II and carbachol

1994 ◽  
Vol 267 (3) ◽  
pp. R792-R798 ◽  
Author(s):  
N. E. Rowland ◽  
B. H. Li ◽  
A. K. Rozelle ◽  
G. C. Smith
Keyword(s):  
Angiotensin Ii ◽  
Ang Ii ◽  
Angiotensin Receptor ◽  
Preoptic Nucleus ◽  
Median Preoptic Nucleus ◽  
Immunocytochemical Detection ◽  
Organum Vasculosum Laminae Terminalis ◽  
Hypothalamic Nuclei ◽  
At1 Antagonist ◽  
Intracerebroventricular Injections

Rats were given intracerebroventricular injections of either angiotensin II (ANG II) or the cholinomimetic carbachol. Some rats received cotreatment with ANG II antagonists selective for either angiotensin receptor AT1 (losartan) or AT2 (PD-123319, CGP-42112A). One hour later, the rats were killed and the brains processed for immunocytochemical detection of Fos-like immunoreactivity (FLI). ANG II treatment induced strong FLI in the anterior subfornical organ (SFO), median preoptic nucleus (MnPO), organum vasculosum laminae terminalis (OVLT), and supraoptic and paraventricular hypothalamic nuclei (SON, PVH). The AT1 antagonist abolished FLI in all regions normally stimulated by ANG II. The AT2 antagonist PD-123319 reduced FLI in SON and PVH, but CGP-42112A was less effective. Carbachol induced strong FLI in SON, PVH, and MnPO and only moderate FLI in SFO and OVLT. The AT1 antagonist prevented carbachol-induced FLI in the MnPO only. The distributions of FLI are compared between these central dipsogens and with that previously reported after peripheral infusion of ANG II, and their implications for mapping central thirst pathways are discussed.

ANG II in median preoptic nucleus and pressor responses to CSF sodium and high sodium intake in SHR

2001 ◽  
Vol 281 (3) ◽  
pp. H1210-H1216 ◽  
Author(s):  
Adam S. Budzikowski ◽  
Frans H. H. Leenen
Keyword(s):  
Wistar Rats ◽  
Sodium Intake ◽  
High Salt ◽  
Ang Ii ◽  
Preoptic Nucleus ◽  
High Sodium ◽  
Median Preoptic Nucleus ◽  
High Sodium Intake ◽  
Air Jet ◽  
Pressor Responses

Pressor responses to increases in cerebrospinal fluid (CSF) sodium in Wistar rats and to high salt intake in spontaneously hypertensive rats (SHR) involve both brain ouabainlike activity (“ouabain”) and the brain renin-angiotensin system (RAS). Because some of the effects of “ouabain” are mediated by the median preoptic nucleus (MnPO) and this nucleus contains all elements of the RAS, the present study assessed possible interactions of “ouabain” and ANG II in this nucleus. In conscious Wistar rats, injection of ANG II into the MnPO significantly increased mean arterial pressure (MAP) and heart rate (HR). This response was not affected by pretreatment with a subpressor dose of ouabain. MAP and HR increases by ouabain in the MnPO were significantly attenuated by MnPO pretreatment with losartan. In Wistar rats, losartan in the MnPO also abolished pressor and HR responses to intracerebroventricular 0.3 M NaCl and attenuated MAP and HR responses to intracerebroventricular ouabain. Five weeks of a high-salt diet in SHRs resulted in exacerbation of hypertension and increased responses to air-jet stress and intracerebroventricular guanabenz. Losartan injected into the MnPO reversed the salt-sensitive component of the hypertension and normalized the depressor response to guanabenz but did not change responses to air-jet stress. We conclude that in the MnPO, ANG II via AT1 receptors mediates cardiovascular responses to an acute increase in CSF sodium as well as the chronic pressor responses to high sodium intake in SHR.

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