Effect of individual or combined ablation of the nuclear groups of the lamina terminalis on water drinking in sheep.
(1/93)
The subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT), and median preoptic nucleus (MnPO) were ablated either individually or in various combinations, and the effects on drinking induced by either intravenous infusion of hypertonic 4 M NaCl (1.3 ml/min for 30 min) or water deprivation for 48 h were studied. Ablation of either the OVLT or SFO alone did not affect drinking in response to intravenous 4 M NaCl, although combined ablation of these two circumventricular organs substantially reduced but did not abolish such drinking. Ablation of the MnPO or MnPO and SFO together also substantially reduced, but did not abolish, drinking in response to intravenous hypertonic NaCl. Only near-total destruction of the lamina terminalis (OVLT, MnPO, and part or all of the SFO) abolished acute osmotically induced drinking. The large lesions also reduced drinking after water deprivation, whereas none of the other lesions significantly affected such drinking. None of these lesions altered feeding. The results show that all parts of the lamina terminalis play a role in the drinking induced by acute increases in plasma tonicity. The lamina terminalis appears to play a less crucial role in the drinking response after water deprivation than for the drinking response to acute intravenous infusion of hypertonic saline. (+info)
Neuronal actions of oxytocin on the subfornical organ of male rats.
(2/93)
The aim of this study was to investigate effects of oxytocin (OT) on electrical neuronal activities in rat subfornical organ (SFO) and compare its action with the well-described excitatory effects of blood-borne angiotensin II (ANG II) on the same SFO neurons. With the use of extracellular recordings from spontaneously active neurons in slice preparations of the SFO of male rats, 11.7% of tested neurons (n = 206) were excited and 9.7% were inhibited by superfusion with 10(-6) M OT. Both excitatory and inhibitory effects of OT were dose dependent with similar threshold concentrations and were blocked by a specific OT-receptor antagonist but not by a vasopressin receptor antagonist. Blocking synaptic transmission with low calcium medium suppressed only inhibitory effects of OT. All but one of the OT-sensitive neurons were also excited by superfusion with ANG II at a concentration much lower than required for OT, suggesting that synaptically released OT rather than blood-borne OT alters the activity of SFO neurons in vivo. The results support the hypothesis that neurally released OT may modulate SFO-mediated functions by acting on OT-sensitive neurons. (+info)
Functional evidence for subfornical organ-intrinsic conversion of angiotensin I to angiotensin II.
(3/93)
Using extracellular electrophysiological recording in an in vitro slice preparation, we investigated whether ANG I can be locally converted to the functionally active ANG II within the rat subfornical organ (SFO). ANG I and ANG II (10(-8)-10(-7) M) excited approximately 75% of all neurons tested with both peptides (n = 25); the remainder were insensitive. The increase in firing rate and the duration and the latency of the responses of identical neurons, superfused with equimolar concentrations of ANG I and ANG II, were not different. The threshold concentrations of the ANG I- and ANG II-induced excitations were both 10(-9) M. Inhibition of the angiotensin-converting enzyme by captopril (10(-4) M; n = 8) completely blocked the ANG I-induced excitation, a 10-fold lower dose was only effective in two of four neurons. The AT1-receptor antagonist losartan (10(-5) M; n = 6) abolished the excitation caused by ANG I and ANG II. Subcutaneous injections of equimolar doses of ANG I and ANG II (200 microliters; 2 x 10(-4) M) in water-sated rats similarly increased water intake by 2.4 +/- 0.5 (n = 16) and 2. 7 +/- 0.4 ml (n = 20) after 1 h, respectively. Control rats receiving saline drank 0.07 +/- 0.06 ml under these conditions. Pretreatment with a low dose of captopril (2.3 x 10(-3) M) 10 min before the injection of ANG I caused a water intake of 2.8 +/- 0.5 ml (n = 10), whereas a high dose of captopril (4.6 x 10(-1) M) suppressed the dipsogenic response of ANG I entirely (n = 11). These data provide direct functional evidence for an SFO-intrinsic renin-angiotensin system (RAS) and underline the importance of the SFO as a central nervous interface connecting the peripheral with the central RAS. (+info)
Effects of subfornical organ lesions on acutely induced thirst and salt appetite.
(4/93)
We examined the role of the subfornical organ (SFO) in stimulating thirst and salt appetite using two procedures that initiate water and sodium ingestion within 1-2 h of extracellular fluid depletion. The first procedure used injections of a diuretic (furosemide, 10 mg/kg sc) and a vasodilator (minoxidil, 1-3 mg/kg ia) to produce hypotension concurrently with hypovolemia. The resulting water and sodium intakes were inhibited by intravenous administration of ANG II receptor antagonist (sarthran, 8 micrograms . kg(-1). min(-1)) or angiotensin-converting enzyme inhibitor (captopril, 2.5 mg/h). The second procedure used injections of furosemide (10 mg/kg sc) and a low dose of captopril (5 mg/kg sc) to initiate water and sodium ingestion upon formation of ANG II in the brain. Electrolytic lesions of the SFO greatly reduced the water intakes, and nearly abolished the sodium intakes, produced by these relatively acute treatments. These results contrast with earlier findings showing little effect of SFO lesions on sodium ingestion after longer-term extracellular fluid depletion. (+info)
Effect of injection of L-NAME on drinking response.
(5/93)
The drinking behavior responses to centrally administered N G-nitro-L-arginine methyl ester (L-NAME; 10, 20 or 40 microg/microl), an inhibitor of nitric oxide synthase, were studied in satiated rats, with cannulae stereotaxically implanted into the lateral ventricle (LV) and subfornical organ (SFO). Water intake increased in all animals after angiotensin II (ANG II) injection into the LV, with values of 14.2 +/- 1.4 ml/h. After injection of L-NAME at doses of 10, 20 or 40 microg/microl into the SFO before injection of ANG II (12 ng/microl) into the LV, water intake decreased progressively and reached basal levels after treatment with 0.15 M NaCl and with the highest dose of L-NAME (i.e., 40 microg). The water intake obtained after 40 microg/microl L-NAME was 0.8 +/- 0.01 ml/h. Also, the injection of L-NAME, 10, 20 or 40 microg/microl, into the LV progressively reduced the water intake induced by hypertonic saline, with values of 5.3 +/- 0.8, 3.2 +/- 0.8 and 0.7 +/- 0.01 ml/h, respectively. These results indicate that nitric oxide is involved in the regulation of drinking behavior induced by centrally administered ANG II and cellular dehydration and that the nitric oxide of the SFO plays an important role in this regulation. (+info)
A subthreshold persistent sodium current mediates bursting in rat subfornical organ neurones.
(6/93)
It is widely accepted that while release of amino acid neurotransmitters occurs with relatively high fidelity, peptidergic synapses require clustered bursts of action potentials for optimal transmitter release. Here we describe for the first time the occurrence and mechanisms of bursting by neurones in the subfornical organ (SFO), cells that utilize the peptide angiotensin II (ANG) in neurotransmission in autonomic pathways. In current clamp recording of isolated SFO neurones in vitro, 53 % (n = 74) showed either spontaneous or evoked burst-like discharge patterns. Bursts typically appeared as shifts in bistable membrane potential, with action potentials superimposed on a depolarizing afterpotential (DAP). Similarly, in vivo single unit recordings of identified SFO neurones showed that 9 of 15 neurones fired in bursts. The pattern of bursting, as well as duration of evoked DAPs was strongly dependent upon membrane potential, suggesting that the DAP contributes to burst generation. Based on our previous observation of calcium-sensing receptor (CaR)-activated bursts, we investigated the effects of NPS R-467, an allosteric agonist of the CaR, on evoked DAPs. NPS R-467 (1 microM) potentiated DAP duration throughout the voltage range tested. We observed a dependence of evoked DAPs upon Na+ channels, as shown by sensitivity to tetrodotoxin (0.5 microM) or reduction of external [Na+] from 140 to 40 mM. The duration of DAPs suggested that a persistent Na+ current mediates these events. Voltage-clamp analysis revealed the presence of a subthreshold sodium current, INaP. Pharmacological blockade of INaP with 100 microM lidocaine reduced the duration of evoked DAPs, and inhibited bursting in SFO neurones. Facilitation of INaP with 10 nM anemone toxin (ATX) increased DAP duration and led to marked excitation of bursting cells. These data indicate that INaP is the main current underlying bursting in SFO neurones. Our observations of receptor-mediated facilitation of bursting by SFO neurones represents an intriguing mechanism through which the release of the peptide neurotransmitter ANG may be regulated. (+info)
Anatomical distribution of NPY-like immunoreactivity in the domestic chick brain (Gallus domesticus).
(7/93)
Neuropeptide Y-immunoreactive (NPY-ir) fibers and neurons in the brain of the domestic chick (Gallus domesticus) were described using an immunohistochemical technique. NPY-ir neurons were seen in the lobus parolfactorius; hyperstriatum, neostriatum, paleostriatum, and archistriatum; hippocampal and parahippocampal areas; dorsolateral corticoid area; piriform cortex; two thalamic areas contiguous to the n. rotundus; n. dorsolateralis anterior thalami, pars lateralis, and pars magnocellularis; n. periventricularis hypothalami; n. paraventricularis magnocellularis; regio lateralis hypothalami; n. infundibuli; inner zone of the median eminence; dorsal and lateral portions of the n. opticus basalis; n. raphes; and n. reticularis paramedianus. NPY-ir fibers were seen throughout the entire chick brain, but were more abundant in the hypothalamus where they formed networks and pathways. They were also observed in some circumventricular organs. The anatomical data of the present study regarding the distribution of NPY ir in the chick brain, together with the physiological findings of other studies, suggest that NPY plays a key role in the regulation of the neuroendocrine, vegetative, and sensory systems of birds by acting as a neuromodulator and/or neurotransmitter. (+info)
Elevated blood pressure in transgenic mice with brain-specific expression of human angiotensinogen driven by the glial fibrillary acidic protein promoter.
(8/93)
In addition to the circulatory renin (REN)-angiotensin system (RAS), a tissue RAS having an important role in cardiovascular function also exists in the central nervous system. In the brain, angiotensinogen (AGT) is expressed in astrocytes and in some neurons important to cardiovascular control, but its functional role remains undefined. We generated a transgenic mouse encoding the human AGT (hAGT) gene under the control of the human glial fibrillary acidic protein (GFAP) promoter to experimentally dissect the role of brain versus systemically derived AGT. This promoter targets expression of transgene products to astrocytes, the most abundant cell type expressing AGT in brain. All transgenic lines exhibited hAGT mRNA expression in brain, with variable expression in other tissues. In one line examined in detail, transgene expression was high in brain and low in tissues outside the central nervous system, and the level of plasma hAGT was not elevated over baseline. In the brain, hAGT protein was mainly localized in astrocytes, but was present in neurons in the subfornical organ. Intracerebroventricular (ICV) injection of human REN (hREN) in conscious unrestrained mice elicited a pressor response, which was abolished by ICV preinjection of losartan. Double-transgenic mice expressing the hREN gene and the GFAP-hAGT transgene exhibited a 15-mm Hg increase in blood pressure and an increased preference for salt. Blood pressure in the hREN/GFAP-hAGT mice was lowered after ICV, but not intravenous losartan. These studies suggest that AGT synthesis in the brain has an important role in the regulation of blood pressure and electrolyte balance. (+info)