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Howard Florey Institute of Physiology and Medicine, University of Melbourne, Parkville 3052, Australia
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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The lamina terminalis is situated in the anterior wall of the third ventricle and plays a major role in fluid and electrolyte homeostasis and cardiovascular regulation. The present study examined whether the effects of intracerebroventricular infusion of hypertonic saline and ANG II on renal sympathetic nerve activity (RSNA) were mediated by the lamina terminalis. In control, conscious sheep (n = 5), intracerebroventricular infusions of 0.6 M NaCl (1 ml/h for 20 min) and ANG II (10 nmol/h for 30 min) increased mean arterial pressure (MAP) by 6 ± 1 (P < 0.001) and 14 ± 3 mmHg (P < 0.001) and inhibited RSNA by 80 ± 6 (P < 0.001) and 89 ± 7% (P < 0.001), respectively. Both treatments reduced plasma renin concentration (PRC). Intracerebroventricular infusion of artificial cerebrospinal fluid (1 ml/h for 30 min) had no effect. In conscious sheep with lesions of the lamina terminalis (n = 6), all of the responses to intracerebroventricular hypertonic saline and ANG II were abolished. In conclusion, the effects of intracerebroventricular hypertonic saline and ANG II on RSNA, PRC, and MAP depend on the integrity of the lamina terminalis, indicating that this site plays an essential role in coordinating the homeostatic responses to changes in brain Na+ concentration.
circumventricular organs; intracerebroventricular; renin; sheep; angiotensin
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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SYSTEMIC INFUSION of hypertonic saline causes a coordinated pattern of responses, including drinking, natriuresis, vasopressin release, and inhibition of renin release, which act to return plasma Na+ to normal levels (3, 7, 21, 28). Similar responses are obtained after infusion of hypertonic saline in the cerebrospinal fluid (CSF; see Refs. 1, 17, and 22). Recently, we have shown that central administration of hypertonic saline causes a baroreceptor-independent inhibition of renal sympathetic nerve activity (RSNA; see Ref. 13), indicating that the renal nerves may in part mediate the renal responses to increases in brain Na+. This response was not mimicked by intracerebroventricular infusion of hypertonic sorbitol, indicating that it depended on the increase in NaCl not osmolality (13). Interestingly, central administration of ANG II causes similar responses to hypertonic saline (1, 8, 12), suggesting that these two stimuli may act on the same neural pathways in the brain. The finding that those responses to central infusion of hypertonic saline that have been examined are all inhibited by central administration of the ANG II type 1 receptor antagonist losartan demonstrates that they are probably mediated by a central angiotensinergic pathway (4, 11, 13, 18).
The central sites at which hypertonic saline and ANG act to control body fluid and cardiovascular homeostasis have been examined in a number of species. One of the most important is the lamina terminalis, which is situated in the anterior wall of the third ventricle and consists of the subfornical organ, median preoptic nucleus, and organum vasculosum of the lamina terminalis (OVLT). In rats, ablation of the anteroventral third ventricle region, which includes the ventral part of the lamina terminalis and tissues lateral to this structure, resulted in adipsia and hypernatremia and attenuated drinking and pressor responses to ANG II (5, 10). In goats, ablation of most of the anterior wall of the third ventricle disrupted the antidiuretic responses to central infusion of hypertonic saline and ANG II (2), and, in sheep, selective lesion of the lamina terminalis disrupted the drinking, natriuretic, and antidiuretic responses to systemic hypertonicity (16, 19, 20). The localization of a high density of ANG II receptors in the sheep lamina terminalis (14) and the expression of c-fos in the lamina terminalis of rats after central administration of ANG II (15) provide further evidence that this area plays a major role in the central responses to ANG II.
Previously, we have shown that central administration of hypertonic saline and ANG II caused inhibition of RSNA and increased arterial pressure in conscious sheep (12, 13). The central sites critical for these responses are not known, and the aim of this study was to determine whether the integrity of the lamina terminalis was essential for these responses to intracerebroventricular infusion of hypertonic saline and ANG II.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Adult merino cross ewes (35-45 kg body wt), oophorectomized and with carotid arteries enclosed in skin loops, were housed in individual metabolism cages in association with other sheep. They were not used until they were accustomed to laboratory conditions and human contact. Sheep were fed a diet of oaten chaff (800 g/day containing 90-120 mmol/kg Na+ and 270-380 mmol/kg K+). Access to water was provided at all times except when the responses to infusions of ANG II and hypertonic saline were studied. All experiments were approved by the Animal Experimentation Ethics Committee of the Howard Florey Institute.
Surgical Procedures
Anesthesia was induced by intravenous thiopental sodium (15 mg/kg). After tracheal intubation, the sheep were maintained on 1.5% halothane in air-oxygen (1:1). Animals were placed in a stereotaxic apparatus, and a stainless steel guide tube was implanted over a lateral cerebral ventricle in an aseptic operation (22). Contrast medium (0.5 ml of sodium iophendylate; Iopamiro; Scherring) was injected in the lateral ventricle to enable radiographic visualization of the third ventricle in all planes. After a small hole was drilled in the skull with a dental drill, an electrode (19-gauge stainless steel tubing blocked at one end) was then implanted in the lamina terminalis in six sheep. In three sheep, which acted as controls for the lesion, electrodes were positioned in tissue adjacent to the lamina terminalis. The electrodes were insulated with epoxylite except for the tips, where the length of the uninsulated electrode was 6 mm. The electrode and guide tube were fixed in position with dental acrylic molded around them and four stainless steel screws that had been inserted in the skull. Animals recovered well from surgery as indicated by their general demeanor and their resumption of normal food and water intake within 2 days.After at least 2 wk recovery, a lesion was made by application of a radio frequency current (100 kHz, 12-15 V, 50-60 mA) between the electrode and an indifferent electrode placed under the skin. The electrode tip was heated to 58-60°C, as measured by a thermistor inserted in the tip of the tube that formed the electrode. Apart from hyperventilation, probably due to heating of the preoptic region, no other disturbance or any adverse effect to the animals was noticed. Following the lesion, at least 3-4 wk were allowed to elapse to allow the fluid and electrolyte balance of the animals to reach a steady state before experiments started. At the time of the experiment, five of the sheep were adipsic and were given 1.0-1.5 liters of water daily via a rumen tube to maintain plasma Na+ and osmolality within the normal ranges. One sheep spontaneously drank, and its intake was restricted to 1.0-1.5 l/day to maintain normal levels of plasma Na+ and osmolality. Fluid intake was normal in the sheep with sham lesions.
On the day before implantation of renal nerve electrodes, a sterile Tygon cannula (1.0 mm ID, 1.5 mm OD) was inserted under aseptic conditions 20 cm into the carotid artery, toward the heart, for the measurement of arterial pressure. Under local anesthesia, a sterile polyethylene cannula (1.18 mm ID, 1.7 mm OD) was inserted 25 cm into the jugular vein for the measurement of central venous pressure (CVP), and a second sterile cannula (0.58 mm ID, 0.97 mm OD) was inserted 20 cm into the jugular vein for intravenous infusion. The patency of these cannulas was maintained by infusing heparinized saline (25 U/ml) at 3.0 ml/h from flush devices (TDF-3WC; Biosensors International). The cannulas used for measurement of arterial and venous pressures were connected to pressure transducers (CDXIII; Cobe) tied to the wool on the sheep's back. The signals from the arterial and venous pressure transducers were amplified and calibrated against mercury and water manometers, respectively. The pressure from both transducers was corrected to compensate for the height of the transducers above the level of the heart. Heart level was taken as 64% of the distance from the back to the sternum, which in sheep is the level of the junction of the left atrium with the left atrial appendage. Heart rate (HR) was recorded with a cardiotachometer triggered by the arterial pressure waveform.
In a second procedure, under general anesthesia, the right or left renal artery was exposed via a paracostal retroperitoneal approach. With the aid of a dissection microscope, a renal nerve, the largest if there were several, was identified running along or parallel to the renal artery and was cleared of surrounding fat. The recording electrodes consisted of stainless steel entomological pins (0.05 mm diameter), etched to a fine point, glued into the end of Teflon-coated 25-strand silver-coated copper wires (CZ1174SPC; Cooner, Chatsworth, CA). The exposed point of the electrode (1.5-2.0 mm in length) was inserted obliquely through the nerve sheath, ensuring that the tip was positioned in the center of the nerve. Up to five electrodes were implanted along the exposed length of nerve and fixed in place with cyanoacrylate glue. The wires were looped and exteriorized through the sutured wound, and a stainless steel suture sewn through the skin was used as an earth. Antibiotics (0.4 g procaine benzylpenicillin, 0.5 g dihydrostreptomycin sulfate; Norbrook Laboratories) were administered prophylactically for 3 days postsurgery.
Nerve Recording
Experiments were conducted on standing, conscious sheep. To minimize any effect of surgical stress, experiments were started on the 4th day after implantation of the electrodes. RSNA was recorded differentially between pairs of electrodes, and the pair with the best signal-to-noise ratio was selected. With the use of this technique, signal-to-noise ratios of between 4:1 and 8:1 were obtained on the 4th day postsurgery, and the signal remained useable (>2:1) for a further 7-14 days. The signal was amplified (×100,000) and filtered (band pass 100-1,000 Hz), displayed on an oscilloscope, and passed through an audio amplifier and loud speaker. Spikes above the noise level were detected with a discriminator and counted. Spike counts (in 10-s bins) were plotted on a chart recorder (Gould RS3400), together with mean arterial pressure (MAP), HR, and mean CVP. Data were read from the chart at the times shown in Figs. 1-4 and consisted of a mean of each variable over 2 min.
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Experimental Protocols
Intracerebroventricular infusions. Before infusion into the lateral cerebral ventricles (icv), the cap was removed from the guide tube, and a sterile probe (20-gauge needle with Luer lock fitting) of appropriate length was inserted through the guide tube into a lateral cerebral ventricle. A sterile polyethelene cannula filled with sterile artificial CSF was connected to the probe, and the probe was considered patent if CSF flowed freely in and back from the ventricle. The concentrations of Na+, K+, Ca2+, and Mg2+ (150, 2.8, 1.2, and 1.0 mmol/l, respectively) in artificial CSF were similar to those in normal sheep CSF (22). All solutions for intracerebroventricular infusion were sterilized by filtration though a sterile 0.22-µm filter before administration. Infusions from a syringe pump (Braun) were started after a 10-min stable control period.
Responses to intracerebroventricular infusion of hypertonic saline and ANG II. The responses to intracerebroventricular infusion of hypertonic saline, ANG II (Human Bachem), and artificial CSF were studied in a group of normal sheep (n = 5), a group of sheep with lesions of the lamina terminalis (n = 6), and a group with lesions adjacent to the lamina terminalis (n = 3). RSNA, MAP, HR, and CVP were measured throughout the experiments. Arterial blood samples were collected for measurement of plasma renin concentration (PRC) at the end of the control and infusion periods and 30 min after the end of the infusions.
After a control period, intracerebroventricular artificial CSF containing 0.6 M NaCl was infused at 1 ml/h for 20 min, and recordings were continued for 30 min after the end of the infusion. In the same groups of sheep, the responses to intracerebroventricular ANG II (10 nmol/ml in CSF) infused for 30 min at 1 ml/h, followed by up to 120 min of postinfusion monitoring, were studied. Control experiments in which artificial CSF was infused at 1 ml/h for 30 min, followed by 30 min of postinfusion monitoring, were also performed.Histology. When all of the experimental procedures had been completed, the animals were killed with an intravenous injection of 100 mg/kg pentobarbitone (Lethobarb; Arnold, Reading, UK). The head was perfused via the carotid arteries with 3 liters of isotonic 0.9% NaCl solution followed by 3 liters of 10% formalin in 0.9% NaCl solution. Brains were then removed from the skull, and a block of tissue containing the lesion site was prepared and embedded in paraffin. Sections (20 µm) of this block were cut in the coronal plane on a rotary microtome, and, after mounting on glass slides, they were stained with cresyl violet and covered with coverslips. The site of the lesion was then examined microscopically and mapped by drawing the projected image using a microfilm reader.
Measurement of PRC.
Blood samples were collected from the arterial cannulas in EDTA tubes
that were kept on ice until centrifugation. The separated plasma was
stored at 
20°C until assay. PRC was determined using a modification
of the antibody capture technique by measuring the generation of ANG I
(6).
Statistics
RSNA was expressed as the percentage change from the mean of three readings taken during the control period. The changes in CVP were calculated as the difference from the mean of the three control readings. A two-way ANOVA, repeated measures on one variable (time), and subsequent least significant difference test were used to compare the values obtained from the two groups during and after each of the treatments (Statistica; Statsoft, Tulsa, OK). Results are presented as means ± SE. For all comparisons P < 0.05 was considered significant.| |
RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Responses to Intracerebroventricular Infusion of Hypertonic Saline in Intact and Lesioned Sheep
In five conscious sheep, intracerebroventricular infusion of hypertonic saline (0.6 M NaCl in CSF at 1 ml/h) reduced RSNA by 80 ± 6% over a 20-min infusion (P < 0.001) and increased MAP by 6 ± 1 mmHg (P < 0.001; Fig. 1). Both HR and CVP were unchanged during the infusion. In three sheep with sham lesions, there was a similar fall in RSNA of 77 ± 6% but no significant increase in MAP (+3 ± 2 mmHg). In six sheep with lesions of the lamina terminalis, basal MAP (81 ± 1 mmHg) was similar to the level in the group of intact sheep (80 ± 2 mmHg). However, in the sheep with lesions of the lamina terminalis, both the renal sympathoinhibition and the pressor response to hypertonic saline were abolished (Fig. 1). Intracerebroventricular infusion of artificial CSF had no effect on RSNA, BP, HR, or CVP in any of the groups of sheep.Responses to Intracerebroventricular Infusion of ANG II in Intact and Lesioned Sheep
Intracerebroventricular infusion of ANG II (10 nmol/h) for 30 min caused a profound inhibition of RSNA in normal sheep (P < 0.001; Fig. 2). RSNA was inhibited by 89 ± 7% at the end of the 30-min infusion and was still at this low level 45 min after the end of the infusion. Even at 120 min after the end of the infusion, RSNA was inhibited by 26 ± 7%. Intracerebroventricular infusion of ANG II caused a sustained increase in MAP, reaching 16 ± 2 mmHg above control 15 min after the end of the infusion (P < 0.001; Fig. 2), but there was no change in HR. There was a progressive increase in mean CVP, reaching a maximum of 1.9 ± 0.9 mmHg above control 15 min after the end of the infusion (P < 0.001). In three sheep with sham lesions, intracerebroventricular ANG II (10 nmol/h) caused similar changes (an inhibition of RSNA by 86 ± 8% and an increase in MAP of 12 ± 5 mmHg). In six sheep with lesions of the lamina terminalis, the inhibition of RSNA and the increase in arterial pressure and CVP in response to intracerebroventricular ANG II were abolished.PRC in Intact and Lesioned Sheep
In intact sheep, intracerebroventricular infusion of hypertonic saline reduced PRC from 1.53 ± 0.26 to 0.74 ± 0.11 nmol · l
1 · h1 at the end
of the infusion (P < 0.05), and at 20 min after the infusion PRC was 0.78 ± 0.19 nmol · l1 · h1 (Fig.
3). Intracerebroventricular infusion of
ANG II reduced PRC from 1.01 ± 0.16 to 0.53 ± 0.12 nmol · l1 · h1
(P < 0.05) at the end of the infusion and to 0.37 ± 0.08 nmol · l1 · h1 at
30 min after the infusion. Intracerebroventricular infusion of CSF had
no effect on PRC in the control group of sheep.
In the group of sheep with lesions of the lamina terminalis, basal PRC
was significantly elevated compared with the intact sheep (Fig. 3). In
the control group, before infusion of hypertonic saline, ANG II, and
CSF, the basal levels of PRC were 1.53 ± 0.26, 1.01 ± 0.16, and 1.35 ± 0.29 nmol · l1 · h1,
respectively. In the group with lesions, the equivalent basal PRC
levels were significantly elevated at 4.86 ± 1.41, 5.60 ± 2.27, and 4.75 ± 1.52 nmol · l1 · h1
(P < 0.05). In sheep with lesions of the lamina
terminalis, intracerebroventricular infusion of either hypertonic
saline or ANG II caused no reduction in PRC (4.86 ± 1.24 and
5.25 ± 1.55 nmol · l1 · h1,
respectively). Intracerebroventricular infusion of CSF had no effect on
PRC in the lesioned sheep.
Histology
All six sheep incurred extensive damage to the midline tissue in the anterior wall of the third ventricle, extending ~1 mm on either side of the midline. The median preoptic nucleus and subfornical organ were entirely ablated in all animals. In three of the sheep, the OVLT was completely ablated; in two of the sheep, all but the most ventral part of the OVLT was ablated with ~20% left intact. In the other sheep, only 20% of the OVLT was damaged. The periventricular preoptic region incurred extensive damage. The supraoptic nucleus was undamaged in all animals; the hypothalamic paraventricular nucleus was largely undamaged. Other structures that incurred minor damage were the nucleus of the diagonal band (vertical limb), medial septal nucleus, and anterior hypothalamic region. There was no apparent reason from the localization of the lesion to account for the spontaneous drinking in one sheep. The anterior commissure incurred extensive damage. An example of a representative lesion of the lamina terminalis is shown in Fig. 4. Lesions were produced in three sheep, which unilaterally destroyed tissue close to the lamina terminalis in the diagonal band and medial preoptic region, the lateral septal nucleus, or the lateral preoptic region but left all structures in the lamina terminalis intact.| |
DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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This is the first study to examine the importance of the lamina terminalis in the control of RSNA by brain Na+ and ANG II. The main findings of this study are that lesions of the lamina terminalis abolished the inhibition of RSNA in response to central administration of hypertonic saline and ANG II in conscious sheep. This lesion also abolished the increase in arterial pressure in response to these stimuli. In addition, this study in sheep demonstrated that lesion of the lamina terminalis increased basal renin levels and prevented the inhibition of renin release by these stimuli.
Evidence from other studies indicates that the area of the brain in the anterior wall of the third ventricle plays a major role in the integration of responses to hypertonicity. Lesion of the anterior wall of the third ventricle caused a pronounced reduction in ANG II-induced drinking in rats (5) and adipsia in goats (2). Two of the nuclei within the lamina terminalis, the subfornical organ and OVLT, are circumventricular organs, sites without a blood-brain barrier that are able to detect changes in blood tonicity and the levels of circulating peptide hormones such as ANG II. Selective lesion of the subfornical organ in rats also produced adipsia and prevented the appropriate responses to water deprivation, subcutaneous hypertonic saline, and ANG II (5, 25). In sheep, although complete lesions of the lamina terminalis abolished the drinking response to intravenous hypertonic saline, lesions of individual nuclei reduced but did not abolish drinking (20). This suggests that there is considerable redundancy of this important function within the structures of the lamina terminalis. Further evidence indicating the importance of this whole area in the responses to hypertonicity and ANG II comes from studies in rats using c-fos expression as a marker for neuronal activity. These studies show that neurons throughout the lamina terminalis are activated by increased systemic osmolality and by central administration of ANG II (15, 23).
The present findings demonstrate that, in addition to the control of drinking and vasopressin release, the lamina terminalis has an essential role in the control of RSNA in response to changes in the concentrations of Na+ and ANG II in CSF. Our previous findings that intracerebroventricular infusion of hypertonic sorbitol did not inhibit RSNA or renin release and did not increase arterial pressure (13) suggest that these responses are mediated by Na+ sensors. However, intracarotid administration of hyperosmolar solutions of either NaCl or sorbitol suppress PRC in sheep, indicating a difference between central and systemic administration of these agents (21). Furthermore, our findings that the inhibition of RSNA in response to central infusion of hypertonic saline is mimicked by infusion of ANG II and that both responses are inhibited by central infusion of losartan (12, 13) indicate that the responses to hypertonic saline are mediated via a pathway that contains a central angiotensinergic synapse. Because this lesion prevents the inhibition of RSNA in response to not only intracerebroventricular hypertonic saline but also to intracerebroventricular ANG II, it is likely that this angiotensinergic synapse is located in the lamina terminalis. The observation in sheep that the lamina terminalis contains the highest concentration of ANG II receptors in the brain (14) is supportive evidence that the angiotensinergic synapse is in this site.
It has been proposed that the functions of the renal nerves include the control of renin release and renal Na+ excretion. The observation that intracerebroventricular hypertonic saline and ANG II, which both inhibit RSNA, inhibit renin release and cause natriuresis concur with this proposal (12, 13, 18), although they do not rule out the participation of other efferent mechanisms. The finding that basal renin secretion rate is increased in sheep with lesions of the lamina terminalis is in agreement with previous findings in rats (24). This increase in PRC indicates that the sheep may have been marginally dehydrated at the time of the experiment. With the method used to record RSNA, there is considerable interanimal variation in the size of the signal that depends on the position of the electrode in the nerve. Therefore, it is not possible to obtain an absolute measure of RSNA, so we were unable to determine whether basal RSNA was increased in the sheep with lesions of the lamina terminalis.
There is extensive evidence that ANG II acts at many sites in the brain to influence blood pressure (8, 27). Interestingly, the increases in arterial pressure in response to intracerebroventricular infusion of hypertonic saline and ANG in conscious sheep were abolished by lesion of the lamina terminalis, demonstrating that this site alone is essential for these pressor responses in this species. Similarly, in rats the anterior wall of the third ventricle is thought to be an essential site for the pressor response to ANG II infused in the lateral ventricles (10). In contrast, in rabbits, infusion of ANG II in the lateral ventricle has little effect on arterial pressure, and the pressor actions of ANG II are mediated by receptors in the hindbrain (9). It is possible that ANG has important cardiovascular actions on brainstem sites in sheep, but ANG II infused in the lateral ventricles may not reach these sites in sufficient concentrations to produce a response.
In summary, these studies demonstrate that, in conscious sheep, the inhibition of RSNA in response to central administration of hypertonic saline or ANG II is dependent on the integrity of the lamina terminalis. This region of the brain is also essential for the pressor response and decrease in renin release in response to these stimuli. Previous studies have demonstrated that this brain region mediates the changes in vasopressin release, natriuresis, and drinking in response to hypertonic saline, and the present findings emphasize the crucial role that the lamina terminalis plays in fluid and electrolyte homeostasis and cardiovascular control via its actions on the renal nerves.
Perspectives
It is well established that cells in the lamina terminalis mediate responses such as drinking, vasopressin release, and changes in renal Na+ excretion in response to plasma hypertonicity to return blood Na+ concentration to normal. The present findings extend the notion that the lamina terminalis plays a central role in fluid and electrolyte homeostasis by demonstrating that it is critical for the inhibition of RSNA and increase in MAP that occurs in response to central administration of hypertonic saline and ANG II. For example, in response to an increase in brain Na+ concentration, RSNA is inhibited, leading to natriuresis and a reduction in renin release. Because both hypertonic saline and ANG II cause excitation of neurons in the lamina terminalis, inhibitory neurotransmission must occur at some point in the pathway to the renal nerves. The neural pathway is unknown, but experiments with neurotropic viruses have shown that there are polysynaptic neural links from the renal sympathetic preganglionic neurons to the rostral ventrolateral medulla, paraventricular nucleus of the hypothalamus, and the lamina terminalis (26). This pathway could pass via the paraventricular nucleus to the spinal cord or could include a relay in the rostral ventrolateral medulla; the inhibitory synapse could be at any level of these possible pathways. It is also likely that other pathways from the lamina terminalis are stimulated by an increase in brain Na+, leading to an increase in sympathetic outflow to other vascular beds, which accounts in part for the pressor response to these stimuli.| |
ACKNOWLEDGEMENTS |
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We are grateful to Douglas McNestrie for excellent technical assistance and to Lisa Clark for the measurement of PRC.
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FOOTNOTES |
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This work was supported by the National Heart Foundation of Australia and by an Institute Grant (no. 983001) from the National Health and Medical Research Council of Australia.
Address for reprint requests and other correspondence: C. May, Howard Florey Institute, Univ. of Melbourne, Parkville 3052, Victoria, Australia (E-mail: c.may{at}hfi.unimelb.edu.au).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 5 November 1999; accepted in final form 11 July 2000.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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) and
in 6 sheep with lesions of the lamina terminalis (
)
during intracerebroventricular (icv) infusion of 0.6 M NaCl in
artificial cerebrospinal fluid (CSF) at 1 ml/h. Results are means ± SE. * P < 0.05, ** P < 0.01, and *** P < 0.001, intact vs. lesioned group.
