| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Medical College, University of Nankai, Tianjin 300071, PR China 2 Division of Neuroscience, The Medical School, University of Birmingham, Birmingham B15 2TT, UK
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
(Received 23 June 2006;
accepted after revision 18 September 2006; first published online 28 September 2006)
Corresponding author J. H. Coote: Division of Neuroscience, The Medical School, University of Birmingham, Birmingham B15 2TT, UK. Email: j.h.coote{at}bham.ac.uk
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The study reports results from 20 male homozygous Brattleboro rats (325 ± 10.8 g), which lack vasopressin, and 20 male Long–Evans rats (307 ± 9 g). The Long–Evans rats were used as control animals because this is the strain from which the Brattleboro rat is derived. Animals were anaesthetized with a mixture of urethane and chloralose (650 and 50 mg kg–1, respectively) given I.V. after initial induction with 4% enflurane in oxygen. Anaesthesia was monitored by observing arterial blood pressure (ABP), heart rate (HR), and the absence of corneal and paw-pinch reflexes. An adequate depth of anaesthesia was maintained by regular administration of additional anaesthetic I.V. as required.
For continuous recording of blood pressure, a femoral artery was cannulated with a polyethylene catheter (PE-50 tubing), which was connected to a pressure transducer (Capto SP844, AD Instruments, Chalgrove, Oxfordshire, UK). A femoral vein was cannulated for administration of drugs. Electrocardiogram (ECG) signals were obtained from two platinum wire electrodes inserted under the skin of a forelimb and hindlimb. Blood pressure and ECG signals were amplified and displayed via a PowerLab data acquisition system (AD Instruments). The trachea was cannulated and spontaneous respiration maintained throughout the experiment. The head of the rat was mounted in a stereotaxic instrument (Narishige, London, UK). Rectal temperature was continuously monitored and maintained at 37°C by a heating blanket. At the end of the experiment, the animal was killed by an overdose of anaesthetic (urethane/chloralose I.V.).
Spinal cord perfusion
The spinal subarachnoid space was cannulated for the intrathecal (I.T.) administration of drugs. After the rat was placed in the stereotaxic frame, the atlanto-occipital membrane was exposed by removing the overlying muscle through a mid-line dorsal incision. A laminectomy was performed at C1 to provide clear access for the intrathecal catheter. A 14 cm length of PP-10 tubing (total volume 15 µl) filled with artificial cerebrospinal fluid (ACSF; containing, in g): NaCl, 7.42; KCl, 0.14; KH2PO4, 0.163; CaCl2, 0.22; MgSO4, 0.319; NaHCO3, 2.18; and D-glucose, 1.8; in 1 l distilled water; pH 7.4) was introduced under the dura mater and advanced 5.5 cm caudally along the dorsal surface so that the tip lay over the T10 segment. The position was confirmed on necropsy at the termination of the experiment. Drugs were administered in a volume of 10 µl and washed in with 20 µl of ACSF. Each infusion took up to 1 min. The following drugs were used: L-glutamic acid (Sigma, Poole, UK), kynurenic acid (4-hydroxyquinoline-2-carboxylic acid; Sigma), (Arg8)-vasopressin (Sigma) and V1a antagonist ([ß-mercapto-ß,ß-clyclopentamethylenepropionyl1,-O-Et-Tyr2,Val4,Arg8]-vasopressin; Sigma). Throughout the Results, the amount of drug applied is given by the volume and molar concentration of each injection. The intrathecal application of each drug was repeated three or more times in each test series and repeatability established at ±5% of initial value. All solutions were made immediately prior to use and pH was adjusted to 7.4 with; NaOH or HCL.
Stimulation of PVN
For stimulation of neurones in the PVN, a small hole was drilled in the skull on the left side immediately caudal to bregma to allow vertical placement of a micropipette. Under micrometer control, a glass micropipette was inserted into the left PVN (co-ordinates: 1.3–2.2 mm caudal to bregma, 0.6 mm lateral to the mid-line and 7–8 mm below the surface of the cortex). The glass micropipettes had a tip size of 30–60 µm and were filled with D,L-homocysteic acid (DLH, 200 mM, pH 7.4; Sigma) dissolved in saline and containing 1% Pontamine Sky Blue (PSB) to mark injection sites. To stimulate PVN neurones, 100 nl of DLH (200 mM) was injected under micrometer control using a microlitre syringe (Hamilton, VWR International, Leicester, UK). At least 15 min was allowed between each PVN stimulus and repeatability was considered acceptable at ±5% for all the control tests reported in this study.
At the end of the experiment, the brain was removed and fixed in formalin. Frozen coronal serial sections (60 µm) through the hypothalamus were cut and mounted on gelatinized slides and air dried. Sections were stained in Cresyl Violet. The position of microinjection sites was determined by the location of PSB spots. The locations were reconstructed according to the rat brain atlas of Paxinos & Watson (1986).
Recording of sympathetic nerve activity
The left kidney was exposed retroperitoneally and, with the aid of an operating microscope, a branch of the nerve to the kidney was dissected free and placed on a bipolar electrode made from silver wire. After the conditions for optimal nerve recording had been established, both the nerve and the electrode were covered in paraffin. The neural signals were amplified (gain 5000; Neurolog, Digitimer, Welwyn Garden City, UK), filtered (50 Hz low-frequency cut-off, 3000 Hz high-frequency cut-off; Neurolog), displayed on an oscilloscope and collected for displaying and later analysis using a PowerLab data acquisition system (AD Instruments).
Haemorrhage protocol
After recording stable baseline levels of ABP, HR and RSNA for 15 min, the effect on RSNA of I.T. application of ACSF (10 µl) was tested. Next a mild haemorrhage was produced by withdrawing 1 ml of venous blood into a heparinized syringe over the next 1 min, from a femoral vein. The blood was reinfused 5 min later. After a further 15 min, providing ABP and RSNA had recovered to the control level, a second haemorrhage test was performed.
Following these tests, the effect of intrathecal application of the V1a antagonist or the glutamate antagonist kynurenic acid was tested. The effect of I.T. ACSF on a haemorrhage was tested as a control. Agents were given I.T. 1 min prior to withdrawing the 1 ml of blood from the femoral vein. Following reinfusion of blood, a recovery period of at least 15 min was allowed to elapse before further tests.
Data analysis
Using a PowerLab/8SP AD Instruments processor and Chart v4.0 software (AD Instruments), ABP, RSNA and ECG were generated on-line. All data were digitized at 1 kHz and stored on a Power Macintosh G4 personal computer (Apple) for on-line or off-line processing. Responses of blood pressure to drugs and to stimulation of PVN were expressed as the difference between the average basal value for the period immediately before each dose of drug response. Responses of RSNA to the various drugs and to PVN stimulation were expressed as a percentage change compared with the basal value immediately before each test. For this purpose, the raw nerve signal was passed through a spike discriminator (PowerLab) to remove background noise and then the total nerve activity in spikes per second from when it changed from basal value to when it returned to basal value was computed (PowerLab). The mean value obtained was compared to the mean value during a similar period before each test. Only experiments in which the level of background noise was confirmed at the end of the experiment following terminal anaesthesia are included in this report. All data are expressed as means ± S.E.M. Statistical analysis was performed using a Mann–Whitney U test after first subjecting the data to a two-way repeated measures ANOVA. A P value of < 0.05 was considered statistically significant.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
In each of 10 rats with a mean ABP of 83 ± 3.3 mmHg, the efficacy of selective antagonists on intrathecally applied agonist-evoked increases in RSNA was first tested before examining their effects on changes in RSNA elicited by PVN stimulation.
Intrathecal glutamate (0.2 M, 10 µl) more than doubled RSNA to 132 ± 34.2%, a change that was significantly different from baseline (P < 0.001). When glutamate was preceded by kynurenic acid (4 mM, 10 µl, I.T.) which had no effect on baseline RSNA when given alone, its excitatory effect on RSNA was significantly decreased to 60 ± 10% (P < 0.01; Fig. 1A).
|
Microinjection of DLH (0.2 M, 100 nl) at 10 sites in the PVN (1 in each of the 10 rats; Fig. 2) elicited an increase in RSNA (145.5 ± 30.5%; P < 0.001 compared with baseline; Fig. 1A) An example of raw data from a single test in one rat is shown in Fig. 3A. Preceding PVN stimulation with intrathecal application of the V1a antagonist (0.05 mM, 10 µl) significantly (P < 0.01) reduced the excitatory effect to a change of 28 ± 10.5% in RSNA. In a further series of tests at these same 10 sites in the PVN, an increase in RSNA of 90 ± 15% (P < 0.001 compared with baseline) was elicited by DLH (0.2 M, 100 nl), and these changes were reduced significantly (P < 0.01) to 14 ± 5% following I.T. kynurenic acid (4 mM, 10 µl; Figs 1A and 3A).
|
|
In 10 Brattleboro rats (mean ABP 80 ± 3 mmHg), intrathecal application of glutamate (0.2 M, 10 µl) increased RSNA by 91 ± 15% (P < 0.001 compared with baseline; Fig. 1B), and this was virtually abolished to 10 ± 7% by a preceding intrathecal application of kynurenic acid (2 mM, 10 µl; P < 0.001), at a dose which alone had no significant effect on baseline RSNA (0.8 ± 1% change).
Intrathecal application of vasopressin (0.02 mM, 10 µl) increased RSNA by 46 ± 7% (P < 0.01 compared with baseline; Fig. 1B). Preceding vasopressin with intrathecal V1a antagonist (0.05 mM, 10 µl) reduced the increase in RSNA to 8.4 ± 8.1% (P < 0.01). The V1a antagonist given alone had no significant effect on baseline RSNA (change of 3.6 ± 3.2%).
Neither kynurenic acid nor the V1a antagonist had a significant effect on the RSNA responses to vasopressin or glutamate, respectively.
At one PVN site in each of 10 rats (Fig. 2), where microinjection of DLH (0.2 M, 100 nl) elicited increases in RSNA, the intrathecal application of the V1a antagonist (0.05 mM, 10 µl) caused little change in the RSNA response, it being 89.6 ± 9.5% to PVN activation alone and 79.7 ± 10.6% following the V1a antagonist (Figs 1B and 3B). In contrast, preceding PVN stimulation at these same sites with intrathecal kynurenic acid (2 mM, 10 µl) significantly reduced the RSNA response from 91.7 ± 9.8 to 64.3 ± 12.5% (P < 0.05; Figs 1B and 3B). This 2 mM dose of kynurenic acid did not significantly change baseline RSNA. However, a higher concentration of kynurenic acid (4 mM) abolished the PVN response in RSNA, but this dose given alone reduced baseline RSNA by 40 ± 5% and therefore we have not used these data for statistical comparisons.
The results are summarized in the bar charts in Fig. 1; an example of raw traces from one test series in one rat are shown in Fig. 3B; and the sites in the PVN are illustrated in representative sections shown in Fig. 2.
The effect of mild haemorrhage in Long–Evans rats
In a further 10 Long–Evans rats with a control mean ABP of 108 ± 3 mmHg, removal of 1 ml of venous blood decreased ABP by 9 ± 1 mmHg and significantly (P < 0.01) increased RSNA by 28 ± 4% (Figs 4A and 5A).
|
|
The increase in RSNA in response to haemorrhage (ABP fall of 9 ± 1.5 mmHg) was reduced to 16.3 ± 3.1% (P < 0.05) by prior I.T. application of the V1a antagonist (0.05 mM, 10 µl; Fig. 5A).
Role of glutamate
Similarly, in the same 10 Long–Evans rats, after I.T. kynurenic acid (4 mM), a haemorrhage which reduced ABP by 9.6 ± 1.9 mmHg resulted in a significantly smaller (P < 0.05) increase in RSNA, it now being 15 ± 3.6% above baseline (Fig. 4A).
In all tests, recovery of RSNA to control baseline was documented following reinfusion.
The effect of mild haemorrhage in Brattleboro rats
In a further 10 BB rats with a control mean ABP of 78 ± 3.5 mmHg, removal of 1 ml of venous blood decreased ABP by 7 ± 1.4 mmHg and significantly (P < 0.01) increased RSNA by 63 ± 14.7% (Figs 4B and 5B).
Action of V1a antagonist
Intrathecal administration of the V1a antagonist (0.05 mM, 10 µl) had no significant effect, either on baseline value of ABP or RSNA, or on the effect of haemorrhage, after which ABP fell by 6 ± 1 mmHg and RSNA increased by 57.5 ± 16% (Fig. 5B).
Role of glutamate
In this group of 10 BB rats, I.T. application of a 4 mM dose of kynurenic acid dramatically reduced baseline RSNA by more than 30%. We therefore tested the effect of a 2 mM concentration of kynurenic acid, which alone did not significantly change RSNA but virtually abolished the excitatory effect of I.T. glutamate (0.2 M, 10 µl). Following I.T. kynurenic acid (2 mM, 10 µl), a haemorrhage which reduced ABP by 5.7 ± 2 mmHg caused an increase in RSNA of 21.4 ± 4.9%, which is a significantly (P < 0.01) reduced response compared with control conditions (Fig. 5B).
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Although supraspinal vasopressin neurones are a significant mediator in the activation of RSNA, the present study reveals that in Long–Evans rats, as in Wistar rats (Yang et al. 2002), part of the effect on RSNA of PVN stimulation is subserved by excitation of glutamate receptors in the spinal sympathetic circuits. An important consideration for this conclusion is the demonstration of selectivity of the antagonists. At the doses used, no effect of the V1a antagonist on the response to glutamate was detected, nor was any change observed in the response to vasopressin following kynurenic acid, confirming our previous study in Wistar rats (Yang et al. 2002).
Therefore, it seems most likely that activation of PVN–spinal neurones can lead to release of vasopressin and glutamate, which then act on their respective receptors on spinal sympathetic neurones. The comparative study described here in the Brattlebro rat provides further assurance of the validity of this interpretation. We show that the V1a antagonist given intrathecally to these rats, in which vasopressin is absent, is unable to prevent the sympatho-excitatory action of intrathecally applied glutamate or of PVN stimulation. This was not a dose-related effect because the same concentrataion of the V1a antagonist prevented strong activation of RSNA induced by intrathecal application of vasopressin in these rats. The latter positive direct action of vasopressin in the Brattleboro rats is unsurprising, since it appears that vasopressin receptors are unaltered in this strain despite the lack of vasopressin (Dreifuss et al. 1982).
The question arises of which neurones mediate the PVN stimulation of RSNA in the Brattleboro rat. This study shows for the first time that this effect resulted from the activation of excitatory amino acid (EAA) receptors in the spinal renal sympathetic network, since it was selectively blocked by kynurenic acid applied intrathecally. This action could be dependent on PVN glutamate neurones projecting directly to the spinal cord or due to PVN neurones activating presympathetic neurones in the rostral ventrolateral medulla (RVLM), which then directly innervate spinal sympathetic neurones. Paraventricular nucleus neurones with appropriate connections have been demonstrated (Yang & Coote, 1998; Shafton et al. 1998; Pyner & Coote, 1999, 2000), and RVLM presympathetic neurones are glutaminergic (Morrison et al. 1989; Deuchars et al. 1995; Stornetta et al. 2002), so either or both pathways may participate. However, a further possibility deserves consideration. The 100 nl volume of a high concentration of DLH could have diffused to nearby regions of the hypothalamus and activated neurones outside the borders of the PVN. One such nearby region is the dorsal medial hypothalamic nucleus (DMH), which is known to activate RVLM–spinal neurones (Horiuchi et al. 2004). We consider this possibility unlikely, since centres of histologically identified injection sites all lay less than –2.0 mm from bregma (Fig. 2) and more than 0.6 mm from the rostral pole of the DMH, according to our histology. Segura et al. (1992), using tritiated bicuculline, demonstrated that 90% of solutions microinjected into the hypothalamus, in volumes of less than 100 nl, had a spherical spread of 0.3–0.7 mm. If this is typical, then in the present study DLH may have diffused some 0.35 mm either side of the centre of the most caudal injection sites. This would suggest that levels of DLH reaching the DMH would have been very low, if any at all.
We have previously shown (Pyner et al. 2002; Yang & Coote, 2003, 2006) that the PVN influence on RSNA plays a key role in maintaining blood volume. For example, an acute increase in venous return or brief stimulation of cardiac atrial receptors with expansion of a balloon placed at the vein–atrial junction reflexly causes a reduction in RSNA (Karim et al. 1972; Kaufman et al. 1981; DiBona & Sawin, 1985; DiBona & Kopp, 1987; Pyner et al. 2002; Yang & Coote, 2003), which is mediated via the PVN (Pyner et al. 2002; Yang & Coote, 2003; Kantzides et al. 2005). There is also evidence that this reflex is dependent on GABA inhibition of PVN–renal presympathetic neurones (Yang & Coote, 2003). The PVN is also involved in the response to a reduction in blood volume. We recently showed in the Wistar rat (Yang & Coote, 2006) and confirmed here in the Long–Evans rat that removal of 1 ml of venous blood reflexly leads to an increase in RSNA mediated partly by supraspinal vasopressin neurones which are most likely to originate in the PVN (Sawchenko & Swanson, 1982; Cechetto & Saper, 1988; Hallbeck & Blomquist, 1999; Huang & Weiss, 1999; Motawei et al. 1999). These neurones are probably the same PVN vasopressin sympatho-excitatory neurones activated by DLH microinjected into the PVN. However, in both Long–Evans and Wistar rats, part of the increase in RSNA in response to hypovolaemia was dependent on activation of spinal EAA receptors, as was the effect of PVN stimulation. The similarity may suggest that the reflex EAA pathway also involves the PVN. Some support for this interpretation is provided by the study of the Brattleboro rat. In these vasopressin-deficient rats, hypovolaemia induced an increase in RSNA that was only reduced by the EAA receptor antagonist kynurenic acid. Therefore, in the absence of vasopressin, the volume reflex regulation of RSNA in these rats is solely dependent on a supraspinal EAA pathway. Since the evidence from genetically unaltered rats strongly indicates that the main afferent pathway for signals from cardiopulmonary volume receptors is via the PVN (Lovick & Coote, 1988; Badoer et al. 1993, 1997; Pyner et al. 2002; Yang & Coote, 2003; Kantzides et al. 2005), we suggest that the supraspinal EAA pathway for the hypovolaemic reflex increase in RSNA in Brattleboro rats also originates in the PVN.
A further interesting observation in this study was that the increase in RSNA following removal of 1 ml of venous blood was some two times greater in the Brattleboro rat even though the fall in blood pressure was of similar magnitude to that in Long–Evans rats. This is in accordance with the observation by Zerbe et al. (1982) that haemorrhage induced a substantially larger increase in plasma noradrenaline and adrenaline (reflecting sympathetic nerve activity) in Brattleboro rats compared with matched control Long–Evans rats. The explanation for the apparent increase in sensitivity of the RSNA response to volume depletion in Brattleboro rats may depend on these rats being slightly hypertonic and dehydrated, conditions to which they are prone (Valtin & Schroeder, 1964). This may have been the reason for the lower blood pressure of these rats in this study. It is nonetheless clear that the absence of vasopressin from PVN neurones projecting to extrahypothalamic cardiovascular nuclei in Brattleboro rats does not appear to lead to deficiency in the neural components of the volume reflex regulation of RSNA, at least in the short term, which may explain in part the observation of diuresis induced by atrial stretch in Brattleboro rats (Kaufman & Stelfox, 1987). This is in contrast to the neuroendocrine deficiency of plasma vasopressin in these rats, which strongly compromises water reabsorption and systemic blood pressure recovery following haemorrhage (Zerbe et al. 1982).
In conclusion, we have confirmed that PVN–spinal vasopressin neurones excite renal sympathetic neurones and play a significant role in the acute response to mild haemorrhage. Furthermore, the effects of both direct activation of PVN neurones and reflexly induced changes in RSNA are in part mediated by spinal EAA receptors. In the Brattleboro rat, the central supraspinal EAA pathway is able acutely to compensate for a vasopressin deficiency. This raises the intriguing possibility that in normal, healthy rats, the vasopressin input to spinal sympathetic neurones has been conserved in order to maintain homeostasis when an animal is exposed to long-term stressors.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Badoer E, McKinley MJ, Oldfield BJ & McAllen RM (1993). A comparison of hypotensive and non-hypotensive haemorrhage on Fos expression in spinally projecting neurones of the paraventricular nucleus and rostral ventrolateral medulla. Brain Res 610, 216–223.[CrossRef][Medline]
Cechetto DF & Saper CB (1988). Neurochemical organisation of the hypothalamic projection to the spinal cord in the rat. J Comp Neurol 272, 579–604.[CrossRef][Medline]
Deuchars SA, Morrison SF & Gilbey MP (1995). Medullary-evoked EPSPs in neonatal rat sympathetic preganglionic neurones in vitro. J Physiol 487, 453–463.
DiBona GF & Kopp UC (1987). Neural control of renal function. Physiol Rev 77, 75–197.
DiBona GF & Sawin LL (1985). Renal nerve activity in conscious rats during volume expansion and depletion. Am J Physiol Renal Physiol 248, F15–F23.
Dreifuss JJ, Muhlethaler M & Gahwiler BH (1982). Electrophysiology of vasopressin in normal rats and in rats of the Brattleboro strain. Ann NY Acad Sci 394, 689–702.[CrossRef][Medline]
Hallbeck M & Blomquist A (1999). Spinal cord-projecting vasopressinergic neurones in the rat paraventricular hypothalamus. J Comp Neurol 411, 201–211.[CrossRef][Medline]
Horiuchi J, McAllen RM, Allen AM, Killinger S, Fontes MAP & Dampney RAL (2004). descending vasomotor pathways from the dorsomedial hypothalamic nucleus: role of medullary raphe and RVLM. Am J Physiol 287, R824–R832.
Hosoya Y, Matsukawa M, Okado N, Sugiara Y & Kohnok K (1995). Oxytocinergic innervation to the upper thoracic sympathetic preganglionic neurones in the rat: a light and electron microscopical study using a combined retrograde transport and immunocytochemical technique. Exp Brain Res 107, 9–16.[Medline]
Huang J & Weiss ML (1999). Characterisation of the central cell groups regulating the kidney in the rat. Brain Res 845, 77–91.[CrossRef][Medline]
Kantzides A, Owens NC, DeMatteo R & Badoer E (2005). Right atrial stretch activates neurons in autonomic brain regions that project to the rostral ventrolateral medulla in the rat. Neuroscience 133, 775–786.[CrossRef][Medline]
Karim F, Kidd C, Malpus CM & Penna PE (1972). The effects of stimulation of the left atrial receptors on sympathetic efferent nerve activity. J Physiol 227, 243–260.
Kaufman S, MacKay B & Kappagoda CT (1981). Effect of stretching the superior vena cava on heart rate in rats. Am J Physiol Heart Circ Physiol 241, H248–H254.
Kaufman S & Stelfox J (1987). Atrial stretch-induced diuresis in Brattleboro rats. Am J Physiol Regul Integr Comp Physiol 252, R503–R506.
Lovick TA & Coote JH (1988). Effects of volume loading on paraventriculo-spinal neurones in the rat. J Auton Nerv Syst 25, 135–140.[CrossRef][Medline]
Ma RC & Dun NJ (1985). Vasopressin depolarises lateral horn cells of the neonatal rat spinal cord in vitro. Brain Res 348, 46–43.
Malpas SC & Coote JH (1994). Role of vasopressin in sympathetic response to paraventricular nucleus stimulation in anaesthetised rats. Am J Physiol 266, R228–R236.[Medline]
Morrison SF, Ernsberger P, Milner TA, Callaway J, Gong A & Reis DJ (1989). A glutamate mechanism in the intermediolateral nucleus mediates sympathoexcitatory responses to stimulation of the rostral ventrolateral medulla. Prog Brain Res 81, 159–169.[Medline]
Motawei K, Pyner S, Ranson RN, Kamel M & Coote JH (1999). Terminals of paraventricular spinal neurones are closely associated with adrenal medullary sympathetic preganglionic neurones: immunocytochemical evidence for vasopressin as a possible neurotransmitter in this pathway. Exp Brain Res 126, 68–76.[CrossRef][Medline]
Paxinos G & Watson C (1986). The Rat Brain in Stereotaxic Coordinates. Academic Press, Orlando, FL, USA.
Pittman QJ, Riphagen CL & Lederis K (1984). Release of immunoassayable neurohypophyseal peptides from rat spinal cord in vivo. Brain Res 300, 321–326.[CrossRef][Medline]
Porter JP & Brody MJ (1986). Spinal vasopressin mechanisms of cardiovascular regulation. Am J Physiol Regul Integr Comp Physiol 251, R510–R517.
Pyner S & Coote JH (1999). Identification of an efferent projection from the paraventricular nucleus of the hypothalamus terminating close to spinally projecting rostral ventrolateral medullary neurons. Neuroscience 88, 949–957.[CrossRef][Medline]
Pyner S & Coote JH (2000). Identification of branching paraventricular neurones of the hypothalamus that project to the rostroventrolateral medulla and spinal cord. Neuroscience 100, 549–556.[CrossRef][Medline]
Pyner S, Deering J & Coote JH (2002). Right atrial stretch induces renal nerve inhibition and c-Fos expression in parvocellular neurones of the paraventricular nucleus in rats. Exp Physiol 87, 25–32.[Abstract]
Ranson RN, Motawei K, Pyner S & Coote JH (1998). The paraventricular nucleus of the hypothalamus sends efferents to the spinal cord of the rat that closely appose sympathetic preganglionic neurones projecting to the stellate ganglion. Exp Brain Res 120, 164–172.[CrossRef][Medline]
Riphagen CL & Pittman QJ (1989a). Mechanisms underlying the cardiovascular responses to intrathecal vasopressin administration in rats. Can J Physiol Pharmacol 67, 269–275.[Medline]
Riphagen CL & Pittman QJ (1989b). Spinal arginine vasopressin elevates renal nerve activity in the rat. J Neuroendocrinol 1, 339–344.[CrossRef]
Sawchenko PE & Swanson LW (1982). Immunohistochemical identification of neurons in the paraventricular nucleus of the hypothalamus that project to the medulla or to the spinal cord in the rat. J Comp Neurol 205, 260–272.[CrossRef][Medline]
Segura T, Martin DS, Sheridan PJ & Haywood JR (1992). Measurement of the distribution of [3H] bicuculline microinjected into the rat hypothalamus. J Neurosci Meth 41, 175–186.[CrossRef][Medline]
Sermasi E & Coote JH (1994). Oxytocin acts at V1a receptors to excite sympathetic preganglionic neurones in neonate rat spinal cord in vitro. Brain Res 647, 323–332.[CrossRef][Medline]
Shafton AD, Ryan A & Badoer E (1998). Neurons in the hypothalamic paraventricular nucleus send collaterals to the spinal cord and to the rostral ventrolateral medulla in the rat. Brain Res 801, 239–243.[CrossRef][Medline]
Stornetta RL, Sevigny CP, Schriehofer AM, Rosin DL & Guyenet PG (2002). Vesicular glutamate transporter DNP1/GLUT2 is expressed by both C1 adrenergic and nonaminergic presympathetic vasomotor neurones of the rat medulla. J Comp Neurol 444, 207–220.[CrossRef][Medline]
Valtin H & Schroeder HA (1964). Familial hypothalamic diabetes insipidus in rats (Brattleboro strain). Am J Physiol 206, 425–430.
Yang Z & Coote JH (1998). Influence of the hypothalamic paraventricular nucleus on cardiovascular neurons in the rostral ventrolateral medulla of the rat. J Physiol 513, 521–530.
Yang Z & Coote JH (2003). Role of GABA and NO in the paraventricular nucleus-mediated reflex inhibition of renal sympathetic nerve activity following stimulation of right atrial receptors in the rat. Exp Physiol 88, 335–342.[Abstract]
Yang Z & Coote JH (2006). The role of supraspinal vasopressin and glutamate neurones in an increase in renal sympathetic activity in response to mild haemorrhage in the rat. Exp Physiol 91, 791–797.
Yang Z, Wheatley M & Coote JH (2002). Neuropeptides, amines and amino acids as mediators of the sympathetic effects of paraventricular nucleus activation in the rat. Exp Physiol 87, 663–674.[Abstract]
Zerbe RL, Feuerstein G, Meyer DK & Kopin IJ (1982). Cardiovascular, sympathetic and renin-angiotensin system responses to haemorrhage in vasopressin-deficient rats. Endocrinology 111, 608–613.[Abstract]
|
Acknowledgements |
|---|
This article has been cited by other articles:
|
|
 |
|
  T. Zhang, Z. Yang, and J. H. Coote Autonomic Neuroscience: Cross-sample entropy statistic as a measure of complexity and regularity of renal sympathetic nerve activity in the rat Exp Physiol, July 1, 2007; 92(4): 659 - 669. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
