Experimental Physiology Email Content Delivery
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Experimental Physiology 92.4 pp 671-676
DOI: 10.1113/expphysiol.2007.037457
© The Physiological Society 2007
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
92/4/671    most recent
expphysiol.2007.037457v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Womack, M. D.
Right arrow Articles by Barrett-Jolley, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Womack, M. D.
Right arrow Articles by Barrett-Jolley, R.
Autonomic Neuroscience

Activation of paraventricular nucleus neurones by the dorsomedial hypothalamus via a tachykinin pathway in rats

 Matthew D. Womack1 and Richard Barrett-Jolley1

1 Department of Veterinary Preclinical Sciences, Veterinary Sciences Building, Brownlow Hill & Crown Street, University of Liverpool, Liverpool L69 7ZJ, UK


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
The dorsomedial hypothalamus (DMH) innervates the paraventricular nucleus (PVN) with substance P (SP) immunoreactive neurones. The PVN itself powerfully influences both the neuroendocrine and the cardiovascular systems. In this in vitro study, we examine the DMH-to-PVN pathway electrophysiologically. Glutamate application to the DMH increased action current frequency in the PVN. This effect was prevented by the glutamate antagonist kynurenic acid or by synaptic block with a high-Mg2+ low-Ca2+ buffer solution. Crucially, the selective tachykinin NK1 receptor antagonist L-703606 also inhibited DMH-to-PVN neurotransmission. Thus we show, for the first time, an excitatory connection between the DMH and PVN that uses tachykinin NK1 receptors. This pathway may be important for the hypothalamic control of neuroendocrine and/or cardiovascular function.

(Received 21 February 2007; accepted after revision 10 April 2007; first published online 27 April 2007)
Corresponding author R. Barrett-Jolley: Department of Veterinary Preclinical Sciences, Veterinary Sciences Building, Brownlow Hill & Crown Street, University of Liverpool, Liverpool L69 7ZJ, UK. Email: rbj{at}liverpool.ac.uk


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Evidence suggests that the substance P (SP) family of neuropeptide neurotransmitters (the ‘tachykinins’) play a major role in cardiovascular control and the expression of a stress response (Chowdrey et al. 1995; Hwang et al. 2005; Culman et al. 1995). During stress, SP content in the dorsomedial hypothalamus (DMH) is reduced (Siegel et al. 1987) whereas paraventricular nucleus (PVN) SP concentration is increased (Chowdrey et al. 1995). Furthermore, central action of tachykinins has been shown to increase sympathetic activity, blood pressure (Culman et al. 1995; Culman & Unger, 1995; Nakayama et al. 1992; Takano et al. 1993) and heart rate (Culman et al. 1995; Culman & Unger, 1995). At least some of this activity originates at the level of the hypothalamus (Culman & Unger, 1995; Culman et al. 1995). Two major hypothalamic nuclei important for integration of physiological responses to stress are the DMH and the PVN (Swanson & Sawchenko, 1983; Spyer, 1994; Badoer, 1996; Fontes et al. 2001; Coote, 2005). For example, c-fos expression in the rat PVN following air jet stress is powerfully reduced by pre-injection of the GABAA agonist muscimol into the DMH (Morin et al. 2001), and stress-evoked increases in adrenocorticotrophic hormone (ACTH) are reduced by injection of muscimol into either the PVN or the DMH (Stotz-Potter et al. 1996a). On the cardiovascular side, PVN neurones are well established to modulate sympathetic outflow (Kannan et al. 1989; Zhang et al. 1997; Zhang & Patel, 1998; Kenney et al. 2001), and the increased sympathetic activity seen during heart failure, for example, is known to involve disrupted GABA control of PVN neurones (Zhang et al. 2001, 2002; Li & Patel, 2003).

SP itself is found at high levels within the PVN (Jessop et al. 1992), and an intrahypothalamic SP pathway projecting from the DMH to the PVN has been identified by means of immunohistochemistry (Bittencourt et al. 1991). In this study, we aimed to investigate whether this tachykinin DMH-to-PVN pathway is excitatory or inhibitory, and to identify the receptors involved.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
Stimulation and recording were conducted on in vitro PVN neurones identified anatomically (Paxinos & Watson, 1986). Experiments were carried out humanely under UK Home Office regulations. Briefly, rats aged 14–16 days were deeply anaesthetized with ether, killed by decapitation and the hypothalamus removed. Hypothalamic slices of rat brain were cut in iced artificial cerebrospinal fluid (ACSF; Zaki & Barrett-Jolley, 2002). In this study, however, 300 µm sagittal slices including the hypothalamus were prepared. Slices were incubated in a modified ACSF at 35–37°C and bubbled with 95% O2–5% CO2, for at least 1 h prior to recording. Slices were perfused at one bath volume per minute with ACSF and maintained at 34–36°C. Neurones were visualized with an upright microscope with near-infrared differential interference contrast (DIC) optics (E600FN Eclipse, Nikon UK).

Pipettes were prepared with thick-walled borosilicate glass (Harvard GC150F). When filled, pipettes had resistances of approximately 10 M{Omega}. Data were recorded with an Axon Axopatch 200B amplifier and low-pass filtered at 5 kHz. Analysis was performed with the PC application, ‘WCP’ (an analysis package written by John Dempster, Strathclyde University, UK).

Action current frequency measurement

The DMH was stimulated by Picospritzer application of glutamate. The puffer pipette was placed approximately 20 µm above the tissue and ejected glutamate against the flow of superfusing ACSF to prevent direct stimulation of the PVN. The experimental set-up is illustrated in Fig. 1. In control experiments, a green (triarylmethane-based) dye was included to further establish that there was no significant leakage of ejectant away from the DMH. Action currents were then recorded in PVN neurones by means of the cell-attached patch technique previously described (Fenwick et al. 1982; Zaki & Barrett-Jolley, 2002). Action current measurements were used to allow quantification of the underlying action potential frequency, without penetration of the cell or rupture of the cell membrane (Fenwick et al. 1982).

Statistics

Statistical testing was performed by StatsDirect (Stats Direct Ltd., Altringham, UK). The P values derive from a Kruskal–Wallis test, with a Conover–Inman multicomparison test unless otherwise stated. A P value of < 0.05 is defined as significant.

Solutions

The ACSF was composed of (mM): NaSO4, 65; NaCHO3, 26; NaCl, 25; glucose, 10; CaCl2, 4; KCl, 1.9; MgSO4, 1.3; and KH2PO4, 1.2; bubbled with 95% O2–5% CO2. The ‘high-Mg2+ low-Ca2+’ solution consisted of (mM): Na2SO4, 65; NaCHO3, 26; NaCl, 25; glucose, 10; CaCl2, 0.5; KCl, 1.9; MgSO4, 10; and KH2PO4, 1.2; bubbled with 95% O2–5% CO2. Pipette solution was (mM): KCl, 140; KOH, 10; Hepes, 10; EGTA, 5; and MgCl2, 1.4. The pH was adjusted to 7.2 with KOH, throughout. With the exception of L-703606 (Tocris, Bristol, UK), a selective NK1 antagonist (Fong et al. 1992), all chemicals and reagents were purchased from Sigma, UK except for the triarylmethane-based dye (SuperCook, Sherburn-in-Elmet, UK).


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
In initial experiments, the action current frequency of PVN neurones recorded with the cell-attached patch was 2.9 ± 0.3 Hz (n = 17). Application of 5 mM glutamate to the DMH resulted in an increase of PVN neurone action current frequency in nine out of 17 neurones; the mean increase was 519 ± 61% (n = 9, P < 0.005, Figs 2A and B). The stimulation of PVN neurones did not represent ‘overflow’ of glutamate, since cutting the hypothalamic slice in between the PVN and the DMH prevented all increase of action current activity (data not shown). In further control experiments, to show that the increase in action current frequency was physiological rather than artefactual (pressure from the Picospritzer, etc.), we applied the broad-specificity excitatory amino acid antagonist kynurenic acid (200 µM) and muscimol (a GABAA agonist; 50 µM). These both caused a significant decrease in basal action current frequency (0.7 ± 0.2 Hz, n = 5, P < 0.005 and 0.0 ± 0.0Hz, n = 7, P < 0.0005, respectively, Fig. 2) and prevented the action of glutamate (0.6 ± 0.1 Hz, n = 5, n.s., Fig. 2C and D, and 0.0 ± 0.0 Hz, n = 7, n.s., Fig. 2E and F, respectively). Synaptic inhibition of the entire pathway by bath application of the high-Mg2+ low-Ca2+ ACSF significantly increased basal action current frequency (7.3 ± 1.1 Hz, n = 6, P < 0.05) and prevented activation of PVN neurones by DMH-applied glutamate (6.3 ± 1.0 Hz. n = 6, n.s., Fig. 2G and H).

We then investigated the tachykinin involvement in the DMH-to-PVN pathway specifically. Direct application of SP to the PVN significantly increased activity of five out of 14 neurones (2-way ANOVA with Bonferroni multiple comparison). In neurones where there was an increase, the mean frequency was increased from 3.2 ± 0.8 to 7.3 ± 1.2 Hz (n = 5, Fig. 3). Locations of reactive and non-reactive neurones to PVN-applied SP and DMH-applied glutamate are shown in Fig. 1. The selective NK1 antagonist L-703606 (1 µM) completely prevented this action (n = 9, Fig. 3). In further experiments, we found that bath application of L-703606 (1 µM) also completely inhibited the increase of PVN action current frequency resulting from glutamate stimulation of the DMH (glutamate alone, 10.7 ± 2.1 Hz; glutamate with L-703606, 1.7 ± 0.5 Hz, n = 5, P < 0.0005, Fig. 4).


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
Two hypothalamic nuclei known to be important sites for integration of the physiological response to stress are the DMH and the PVN (Swanson & Sawchenko, 1983; Spyer, 1994; Badoer, 1996; Stotz-Potter et al. 1996a,b; Morin et al. 2001; Samuels et al. 2002; Coote, 2005). It has been shown that there is an SP-containing neuronal projection from the DMH to the PVN (Bittencourt et al. 1991), and evidence suggests that this pathway may be important for integration of the stress response (Siegel et al. 1987; Chowdrey et al. 1995). Previously, however, there have been no electrophysiological studies on the nature of the DMH-to-PVN connection. We therefore sought to identify the neurotransmitters involved in this pathway. We stimulated the DMH (with glutamate) and recorded action current frequency from the PVN. Our initial experiments show that there is a functional neural connection between the two sites, since stimulation of the DMH fails to excite PVN neurones if the pathway is physically cut, or subjected to synaptic block with a high-Mg2+ low-Ca2+ bath solution.

The DMH-to-PVN pathway was blocked by non-specific excitatory amino acid (ionotopic) receptor inhibition with kynurenic acid. Glutamate clearly acted in (or very near to) the DMH, since: (i) it was applied very discretely by means of a Picospritzer; and (ii) these two nuclei lie approximately 1 mm apart and the physical cut we used to isolate the DMH from the PVN was within 100 µm of the DMH. In the most crucial experiments, we show that bath application of the specific NK1 receptor antagonist L-703606 eliminates the activation of PVN neurones resulting from glutamate application directly to the DMH. This inhibition was reversible and demonstrates the clear presence of an excitatory DMH-to-PVN tachykinin pathway. Furthermore, the activation could be mimicked by direct application of SP to the PVN. In previous experiments, we have shown both the presence of SP receptors and an excitatory SP response in the PVN (Barrett-Jolley, 2003; Womack & Barrett-Jolley, 2004) and so we suggest that tachykinin synapses are likely to be within the PVN itself.

There is strong evidence that the DMH-to-PVN pathway is important for physiological responses to stress (Dimicco et al. 1996; Stotz-Potter et al. 1996a; Morin et al. 2001), and certainly the PVN itself is important for control of both the ACTH (Swanson & Sawchenko, 1983) and the cardiovascular system (Coote, 2005). This pathway could then be important for either the cardiovascular or the neuroendocrine response to stress. Whilst there is evidence to suggest that the PVN is important for the cardiovascular response to stress (specifically, ‘the defence reaction’; Jansen et al. 1995; Duan et al. 1997), there is also evidence that the DMH-to-PVN pathway is more important for the corticotrophin-releasing hormone (CRH) and ACTH responses to stress (‘air stress’; Stotz-Potter et al. 1996a). Immunostaining for CRH is found widely in the PVN, both in parvocellular (Sawchenko & Swanson, 1985; Cai & Wise, 1996) and in magnocellular neurones (Sawchenko & Swanson, 1985); however, in the sagittal preparation used in this study we could not distinguish between these two PVN subpopulations (Fig. 1). It is likely that different stressors result in subtly different pathways and responses, since stress itself can only be loosely defined as a ‘non-specific response of the body to any demand placed upon it’ (Seyle, 1956).

To conclude, the PVN is of profound importance to both sympathetic control and neuroendocrine regulation and we show here, for the first time, that the tachykininergic input from the DMH to the PVN is excitatory and mediated by SP acting at NK1 receptors.


Figure 1
View larger version (20K):
[in this window]
[in a new window]

  		Figure 1.  Schematic diagram summarizing the distribution of PVN neurones responding to glutamate (Glu) application to the DMH ({blacksquare}), or non-responding neurones ({circ})
The diagram also shows neurones responding to exogenously applied SP ({triangleup}); however, for clarity, PVN neurones not responding to exogenous SP are omitted. Anatomical markers were identified following Paxinos & Watson (1986). The location is 0.4 mm lateral of the mid-line. Scale bar represents 4 mm in the main figure and 1 mm in the inset. Note that only those areas shown on the figure are apparent in the neonate.

 

Figure 2
View larger version (33K):
[in this window]
[in a new window]

  		Figure 2.  Glutamate stimulation of the DMH increases action current frequency in the PVN
A, PVN neurone action current frequency trace during application of 5 mM glutamate to the DMH. B, mean data for a number of experiments such as that illustrated in A. C, PVN neurone action current frequency trace during application of 5 mM glutamate to the DMH in the presence of bath-applied glutamate antagonist kynurenic acid (200 µM). D, mean data for a number of experiments such as that illustrated in C. E, PVN neurone action current frequency trace during application of 5 mM glutamate to the DMH in the presence of bath-applied muscimol (50 µM). F, mean data for a number of experiments such as that illustrated in E. G, PVN neurone action current frequency trace during application of 5 mM glutamate to the DMH in the presence of synaptic block by high-Mg2+ low-Ca2+ ACSF (10 mM/0.5 mM; see Solutions subsection in the Methods). H, mean data for a number of experiments such as that illustrated in G. All data and statistical results are given in the text.

 

Figure 3
View larger version (44K):
[in this window]
[in a new window]

  		Figure 3.  Substance P increases PVN neuronal discharge
A, a basal action current frequency trace from a PVN neurone. B, the same PVN neurone as in A, showing the action current frequency trace during direct application (ipo) of 1 µM SP. C, PVN neurone action current frequency in the presence of bath-applied NK1 receptor antagonist L-703606 (1 µM). D, the same PVN neurone as in C, in the presence of L-703606 and SP, both at 1 µM.E, mean data from the 5/14 PVN neurones which did respond to SP, such as those shown in A and B. F, mean data from a number of experiments such as those shown in C and D. All data and statistical results are given in the text.

 

Figure 4
View larger version (18K):
[in this window]
[in a new window]

  		Figure 4.  The DMH-to-PVN pathway involves tachykinin NK1 receptors
A, PVN neurone action current frequency trace during application of 5 mM glutamate to the DMH. B, PVN neurone action current frequency trace during application of 5 mM glutamate to the DMH in the presence of the highly selective NK1 antagonist L-703606 (bath applied, 1 µM). C, the same cell as shown in B, following washout of L-703606. D, mean data for a number of experiments such as that shown in A, B and C. All data and statistical results are given in the text.

 

   Footnotes
 
Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial explotation.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Badoer E (1996). Cardiovascular role of parvocellular neurones in the PVN of the hypothalamus. News Physiol Sci 11, 43–47.[Abstract/Free Full Text]

Barrett-Jolley R (2003). Substance P inhibits GABAA currents of paraventricular spinally projecting neurones. Br Neurosci Abstracts 17, P33.01.

Bittencourt JC, Benoit R & Sawchenko PE (1991). Distribution and origins of substance-P-immunoreactive projections to the paraventricular and supraoptic nuclei – partial overlap with ascending catecholaminergic projections. J Chem Neuroanat 4, 63–78.[CrossRef][Medline]

Cai AH & Wise PM (1996). Age-related changes in the diurnal rhythm of CRH gene expression in the paraventricular nuclei. Am J Physiol 270, E238–E243.[Medline]

Chowdrey HS, Larsen PJ, Harbuz MS, Lightman SL & Jessop DS (1995). Endogenous substance-P inhibits the depression of corticotropin-releasing hormone during a chronic inflammatory stress. Life Sci 57, 2021–2029.[CrossRef][Medline]

Coote JH (2005). A role for the paraventricular nucleus of the hypothalamus in the autonomic control of heart and kidney. Exp Physiol 90, 169–173.[Abstract/Free Full Text]

Culman J, Itoi K & Unger T (1995). Hypothalamic tachykinins. Mediators of stress responses? Ann NY Acad Sci 771, 204–218.[CrossRef][Medline]

Culman J & Unger T (1995). Central tachykinins: mediators of defence reaction and stress reactions. Can J Physiol Pharmacol 73, 885–891.[Medline]

DiMicco JA, Stotz-Potter EH, Monroe AJ & Morin SM (1996). Role of the dorsomedial hypothalamus in the cardiovascular response to stress. Clin Exp Pharmacol Physiol 23, 171–176.[Medline]

Duan YF, Winters R, McCabe PM, Green EJ, Huang Y & Schneiderman N (1997). Cardiorespiratory components of defense reaction elicited from paraventricular nucleus. Physiol Behav 61, 325–330.[CrossRef][Medline]

Fenwick EM, Marty A & Neher E (1982). A patch-clamp study of bovine chromaffin cells and of their sensitivity to acetylcholine. J Physiol 331, 577–597.[Abstract/Free Full Text]

Fong TM, Huang RR & Strader CD (1992). Localization of agonist and antagonist binding domains of the human neurokinin-1 receptor. J Biol Chem 267, 25664–25667.[Abstract/Free Full Text]

Fontes MAP, Tagawa T, Polson JW, Cavanagh SJ & Dampney RAL (2001). Descending pathways mediating cardiovascular response from dorsomedial hypothalamic nucleus. Am J Physiol Heart Circ Physiol 280, H2891–H2901.[Abstract/Free Full Text]

Hwang BH, Katner J & Iyengar S (2005). Corticotropin releasing factor mRNA and substance P receptor binding in the paraventricular hypothalamic nucleus, central nucleus of the amygdala, and locus coeruleus of Sprague-Dawley rats following restraint-induced stress. J Mol Neurosci 25, 239–250.[CrossRef][Medline]

Jansen AS, Nguyen XV, Karpitskiy V, Mettenleiter TC & Loewy AD (1995). Central command neurons of the sympathetic nervous system: basis of the fight-or-flight response. Science 270, 644–646.[Abstract/Free Full Text]

Jessop DS, Chowdrey HS, Larsen PJ & Lightman SL (1992). Substance P – multifunctional peptide in the hypothalamopituitary system. J Endocrinol 132, 331–337.[Medline]

Kannan H, Hayashida Y & Yamashita H (1989). Increase in sympathetic outflow by paraventricular nucleus stimulation in awake rats. Am J Physiol Regul Integr Comp Physiol 256, R1325–R1330.[Abstract/Free Full Text]

Kenney MJ, Weiss ML, Patel KP, Wang Y & Fels RJ (2001). Paraventricular nucleus bicuculline alters frequency components of sympathetic nerve discharge bursts. Am J Physiol Heart Circ Physiol 281, H1233–H1241.[Abstract/Free Full Text]

Li YF & Patel KP (2003). Paraventricular nucleus of the hypothalamus and elevated sympathetic activity in heart failure: the altered inhibitory mechanisms. Acta Physiol Scand 177, 17–26.[CrossRef][Medline]

Morin SM, Stotz-Potter EH & DiMicco JA (2001). Injection of muscimol in dorsomedial hypothalamus and stress-induced Fos expression in paraventricular nucleus. Am J Physiol Regul Integr Comp Physiol 280, R1276–R1284.[Abstract/Free Full Text]

Nakayama Y, Takano Y, Saito R & Kamiya H (1992). Central pressor actions of tachykinin NK-3 receptor in the paraventricular nucleus of the rat hypothalamus. Brain Res 595, 339–342.[CrossRef][Medline]

Paxinos G & Watson C (1986). The Rat Brain in Stereotaxic Coordinates, 2nd edn. Academic Press Inc., London.

Samuels BC, Zaretsky DV & DiMicco JA (2002). Tachycardia evoked by disinhibition of the dorsomedial hypothalamus in rats is mediated through medullary raphe. J Physiol 538, 941–946.[Abstract/Free Full Text]

Sawchenko PE & Swanson LW (1985). Localization, colocalization, and plasticity of corticotropin-releasing factor immunoreactivity in rat-brain. Fed Proc 44, 221–227.[Medline]

Seyle H (1956). The Stress of Life. McGraw-Hill, New York.

Siegel RA, Duker EM, Pahnke U & Wuttke W (1987). Stress-induced changes in cholecystokinin and substance P concentrations in discrete regions of the rat hypothalamus. Neuroendocrinology 46, 75–81.[Medline]

Spyer KM (1994). Annual review prize lecture. Central nervous mechanisms contributing to cardiovascular control. J Physiol 474, 1–19.[Free Full Text]

Stotz-Potter EH, Morin SM & DiMicco JA (1996a). Effect of microinjection of muscimol into the dorsomedial or paraventricular hypothalamic nucleus on air stress-induced neuroendocrine and cardiovascular changes in rats. Brain Res 742, 219–224.[CrossRef][Medline]

Stotz-Potter EH, Willis LR & DiMicco JA (1996b). Muscimol acts in dorsomedial but not paraventricular hypothalamic nucleus to suppress cardiovascular effects of stress. J Neurosci 16, 1173–1179.[Abstract/Free Full Text]

Swanson LW & Sawchenko PE (1983). Hypothalamic integration – organization of the paraventricular and supraoptic nuclei. Ann Rev Neurosci 6, 269–324.[CrossRef][Medline]

Takano Y, Nakayama Y, Matsumoto T, Saito R & Kamiya H (1993). The mechanism of central pressor actions of tachykinin NK-3 receptor in the paraventricular nucleus of the hypothalamus in rats. Regul Pept 46, 360–363.[CrossRef][Medline]

Womack MD & Barrett-Jolley R (2004). Tachykinin receptor-mediated inhibition of GABAA currents in parvocellular neurones of the rat paraventricular nucleus. J Physiol 567.P, PC141.

Zaki A & Barrett-Jolley R (2002). Rapid neuromodulation by cortisol in the rat paraventricular nucleus: an in vitro study. Br J Pharmacol 137, 87–97.[CrossRef][Medline]

Zhang K, Li YF & Patel KP (2001). Blunted nitric oxide-mediated inhibition of renal nerve discharge within PVN of rats with heart failure. Am J Physiol Heart Circ Physiol 281, H995–H1004.[Abstract/Free Full Text]

Zhang K, Li YF & Patel KP (2002). Reduced endogenous GABA-mediated inhibition in the PVN on renal nerve discharge in rats with heart failure. Am J Physiol Regul Integr Comp Physiol 282, R1006–R1015.[Abstract/Free Full Text]

Zhang K, Mayhan WG & Patel KP (1997). Nitric oxide within the paraventricular nucleus mediates changes in renal sympathetic nerve activity. Am J Physiol Regul Integr Comp Physiol 42, R864–R872.

Zhang K & Patel KP (1998). Effect of nitric oxide within the paraventricular nucleus on renal sympathetic nerve discharge: role of GABA. Am J Physiol Regul Integr Comp Physiol 44, R728–R734.


   Acknowledgements
 
This work was funded by the British Heart Foundation.





This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
92/4/671    most recent
expphysiol.2007.037457v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Womack, M. D.
Right arrow Articles by Barrett-Jolley, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Womack, M. D.
Right arrow Articles by Barrett-Jolley, R.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS