γ-Aminobutyric Acid
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            Receptor–Mediated Responses in the Nucleus Tractus Solitarius Are Altered in Acute and Chronic Hypertension

Vitela, Melissa; Mifflin, Steve

doi:10.1161/01.hyp.37.2.619

Cited by 39 publications

(39 citation statements)

References 14 publications

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“…Increased nociceptive afferent inputs from the hindlimb increased the expression of the GABA B mRNA in dorsal root ganglia and dorsal regions of the lumbar spinal cord (9), suggesting that synaptic activity can regulate the expression of GABA B receptors. We have reported that HT is associated with an increased expression of GABA B receptor mRNA (3) and provided indirect evidence that this change occurs primarily in postsynaptic, as opposed to presynaptic, elements of the NTS (17). This suggests an enhanced expression of GABA B receptors, and our data further suggest that this expression occurs in MSNs.…”

Section: Discussionsupporting

confidence: 67%

“…Previous studies have demonstrated enhanced responses to NTS microinjection of the GABA B receptor agonist baclofen in this (3,17) and other (15) models of HT. This finding is consistent with the enhanced inhibition of monosynaptic AN-evoked discharge in NTS neurons by iontophoretic application of baclofen.…”

Section: Discussionmentioning

confidence: 51%

“…In several models of HT (e.g., spontaneously hypertensive rats, deoxycorticosterone acetate salt, and renal wrap), an enhanced pressor response to the microinjection of baclofen into the NTS has been observed, whereas responses to GABA A agonists remain the same as in normotensive (NT) rats (3,15,17). In the renal-wrap model of HT, the enhanced pressor response to NTS microinjections of the GABA B receptor agonist baclofen is associated with increased expression of GABA B receptor mRNA (3).…”

mentioning

confidence: 99%

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Hypertension alters GABA receptor-mediated inhibition of neurons in the nucleus of the solitary tract

Mei

Zhang

Mifflin

2003

American Journal of Physiology-Regulatory, Integrative and Comp

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. Hypertension alters GABA receptor-mediated inhibition of neurons in the nucleus of the solitary tract. Am J Physiol Regul Integr Comp Physiol 285: R1276-R1286, 2003 10.1152/ajpregu. 00255.2003.-Previous studies have demonstrated that microinjection of baclofen, a GABA B receptor agonist, into the nucleus of the solitary tract (NTS) results in an enhanced pressor response in hypertensive (HT) rats compared with normotensive (NT) rats, suggesting a possible alteration in the responses of neurons in this area to activation of GABA B receptors. The following studies were designed to determine whether HT alters the sensitivity of neurons in the NTS to GABA receptor agonists. Sham-operated NT and unilateral nephrectomized, renal-wrap HT Sprague-Dawley rats were anesthetized, and the responses of NTS neurons receiving aortic nerve (AN) afferent inputs to iontophoretic application of GABA, the GABA A receptor agonist muscimol, and the GABA B agonist baclofen were examined. The AN input was classified as monosynaptic (MSN) if the cell responded to each of two stimuli separated by 5 ms with an action potential. If the cell did not respond, the input was considered polysynaptic (PSN). In MSNs, inhibition of AN-evoked discharge by GABA was not altered in 1 wk of HT but was reduced in 4 wk of HT, whereas in PSNs, sensitivity to GABA was reduced at 1 and 4 wk of HT. In HT rats, inhibition of AN-evoked discharge by baclofen was enhanced in MSNs, but not in PSNs, after 1 and 4 wk of HT, whereas inhibition by muscimol was reduced in MSNs and PSNs at 1 and 4 wk of HT. Changes in sensitivity to muscimol and baclofen within MSNs were the same whether the MSN received a slowly or a rapidly conducted AN afferent input. The results demonstrate that early in HT the sensitivity of NTS neurons to inhibitory amino acids is altered and that these changes are maintained for Ն4 wk. The alterations are dependent on the subtype of GABA receptor being activated and whether the neuron receives a mono-or polysynaptic baroreceptor afferent input. (12), and GABA B receptors are metabotropic, G protein-coupled receptors that mediate presynaptic and postsynaptic inhibition by reductions in calcium conductance or increases in potassium conductance, respectively (8). Activation of GABA A receptors on NTS neurons results in chloride-dependent membrane hyperpolarization and inhibition of baroreceptor-evoked discharge (10,19). Activation of GABA B receptors can evoke presynaptic and/or postsynaptic inhibition of NTS neurons (1, 19) and inhibit baroreceptor-evoked discharge in NTS neurons (19).The sensitivity of NTS neurons to the selective GABA A agonist muscimol was the same whether the neuron received a monosynaptic or a polysynaptic aortic nerve (AN) input (19). In contrast, NTS neurons receiving a monosynaptic AN input were much less sensitive to the inhibitory effects of the GABA B agonist baclofen than were NTS neurons receiving a polysynaptic AN input (19). An in vitro study reported that presynaptic inhibition of monosynaptic tractus inputs t...

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 51%

mentioning

confidence: 99%

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Hypertension alters GABA receptor-mediated inhibition of neurons in the nucleus of the solitary tract

Mei

Zhang

Mifflin

2003

American Journal of Physiology-Regulatory, Integrative and Comp

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“…The Woodchuck posttranscriptional regulatory element (WPRE) and the presence of a bovine growth hormone polyadenylation sequence ensure high transcription following transduction. Microinjections were performed in an aseptic environment as described previously (10,29) to inject shRNA and scRNA into the NTS of WKY rats under 2% isoflurane anesthesia. To cover the rostralcaudal extent of NTS HSD2 neurons, three injections of the viral construct (100 nl; Ͼ1 ϫ 10 12 genomic particles/ml) were injected 0.5 mm below the surface at calamus scriptorius and bilaterally at 0.5 mm rostral and 0.5 mm lateral to calamus.…”

Section: Methodsmentioning

confidence: 99%

Mineralocorticoid receptor in the NTS stimulates saline intake during fourth ventricular infusions of aldosterone

Koneru

Bathina

Cherry

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Koneru B, Bathina CS, Cherry BH, Mifflin SW. Mineralocorticoid receptor in the NTS stimulates saline intake during fourth ventricular infusions of aldosterone. Am J Physiol Regul Integr Comp Physiol 306: R61-R66, 2014. First published November 20, 2013 doi:10.1152/ajpregu.00434.2013.-The purpose of this study was to determine whether neurons within the nucleus tractus solitarius (NTS) that express the mineralocorticoid receptor (MR) play a role in aldosterone stimulation of salt intake. Adult Wistar-Kyoto (WKY) rats received microinjections into the NTS of a short-hairpin RNA (shRNA) for the MR, to site specifically reduce levels of the MR by RNA interference (shRNA; n ϭ 9) or scrambled RNA as a control (scRNA; n ϭ 8). After injection of the viral construct, aldosteronefilled osmotic minipumps were implanted subcutaneously and connected to a cannula extending into the fourth ventricle to infuse aldosterone at a rate of 25 ng/h. Before and after surgeries, rats had ad libitum access to normal sodium (0.26%) rat chow and two graduated drinking bottles filled with either distilled water or 0.3 M NaCl. Before the surgeries, basal saline intake was 1.6 Ϯ 0.6 ml in the scRNA group and 1.56 Ϯ 0.6 ml in the shRNA group. Twenty-four days postsurgery, saline intake was elevated to a greater extent in the scRNA group (5.9 Ϯ 1.07 ml) than in the shRNA group (2.41 Ϯ 0.6 ml). Post mortem immunohistochemistry revealed a significant reduction in the number of NTS neurons exhibiting immunoreactivity for MR in shRNA-injected rats (23 Ϯ 1 cells/section) versus scRNAinjected rats (33 Ϯ 2 cells/section; P ϭ 0.008). shRNA did not alter the level of 11-␤-hydroxysteroid dehydrogenase type II (HSD2) protein in the NTS as judged by the number of HSD2 immunoreactive neurons. These results suggest that fourth ventricular infusions of aldosterone stimulate saline intake, and that this stimulation is at least in part mediated by hindbrain NTS neurons that express MR.

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“…Other pathways include the cardiopulmonary reflex and blood volume regulation, which also display evidence of a chronic effect on SNA (87,93). In addition, chronic alterations within the central pathways themselves may also regulate the long-term level of SNA (43,59,94).…”

Section: Concluding Remarks and Future Directionsmentioning

confidence: 99%

What sets the long-term level of sympathetic nerve activity: is there a role for arterial baroreceptors?

Malpas

2004

American Journal of Physiology-Regulatory, Integrative and Comp

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Malpas, Simon C. What sets the long-term level of sympathetic nerve activity: is there a role for arterial baroreceptors? Am J Physiol Regul Integr Comp Physiol 286: R1-R12, 2004; 10.1152/ajpregu.00496.2003.-Much of our knowledge of the influence of the sympathetic nervous system on the control of blood pressure is built on experimental approaches that focus very much on time scales Ͻ24 h. Although direct recordings of sympathetic nerve activity (SNA) over short time scales provide important information, it is difficult to place their relevance over the longer term where the development of chronic changes in blood pressure are likely to be a mixture of hormonal, renal, and neural influences. Recently new experimental approaches are now revealing a possible role for arterial baroreceptors in the chronic regulation of SNA. These studies reveal that chronic increases in blood pressure are associated with chronic changes in SNA that may be due to nonresetting of the blood pressure-SNA baroreflex relationship. This review discusses the implications of such information, highlighting new technologies for long-term recording of SNA that appear to hold much promise for revealing the role of SNA to the kidney for the long-term control of blood pressure. blood pressure; baroreflex; renal THE CONTROL OF ARTERIAL PRESSURE is a complex mixture of the long-and short-term influences of hormones, local vascular factors, and neural mechanisms. With regard to neural influences, much progress has been made in recent years on the central nervous system pathways involved in regulating sympathetic nerve activity (SNA) and the effect of that activity on vascular resistance. However, our knowledge of this control is mostly confined to short time scales of seconds and minutes, with a paucity of studies extending their focus to the longer term aspects (Ͼ24 h). Yet such information is liable to be critical in understanding the pathogenesis of hypertension where the onset of the disease is most likely to be a combination of slowly developing factors. As new tools for assessing sympathetic activity over longer time scales emerge, there is a growing desire and ability to understand longer term aspects of the regulation of SNA. It is recognized that pathways involved in regulating blood volume, osmolarity, and oxygen levels, as well as chronic changes in central nervous system function, are all likely to be important factors in understanding how SNA is controlled. However, given the revival in the hypothesis that arterial baroreflexes play a role in regulating the long-term levels of blood pressure, this review concentrates on the recent research supporting this concept. HISTORY

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γ-Aminobutyric Acid _B Receptor–Mediated Responses in the Nucleus Tractus Solitarius Are Altered in Acute and Chronic Hypertension

Cited by 39 publications

References 14 publications

Hypertension alters GABA receptor-mediated inhibition of neurons in the nucleus of the solitary tract

Hypertension alters GABA receptor-mediated inhibition of neurons in the nucleus of the solitary tract

Mineralocorticoid receptor in the NTS stimulates saline intake during fourth ventricular infusions of aldosterone

What sets the long-term level of sympathetic nerve activity: is there a role for arterial baroreceptors?

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γ-Aminobutyric Acid B Receptor–Mediated Responses in the Nucleus Tractus Solitarius Are Altered in Acute and Chronic Hypertension

Cited by 39 publications

References 14 publications

Hypertension alters GABA receptor-mediated inhibition of neurons in the nucleus of the solitary tract

Hypertension alters GABA receptor-mediated inhibition of neurons in the nucleus of the solitary tract

Mineralocorticoid receptor in the NTS stimulates saline intake during fourth ventricular infusions of aldosterone

What sets the long-term level of sympathetic nerve activity: is there a role for arterial baroreceptors?

Contact Info

Product

Resources

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γ-Aminobutyric Acid _B Receptor–Mediated Responses in the Nucleus Tractus Solitarius Are Altered in Acute and Chronic Hypertension