Enhanced gamma-aminobutyric acid-mediated responses in nucleus tractus solitarius of hypertensive rats.

Tsukamoto, Kazuyoshi; Sved, Alan F.

doi:10.1161/01.hyp.22.6.819

Cited by 55 publications

(43 citation statements)

References 30 publications

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“…Most of the intermediate NTS neurons receive tonic GABA inputs from either interneurons in the NTS or projections from other brain regions (31). There is considerable evidence suggesting that increased GABAergic inhibition in the intermediate NTS contributes to the development of hypertension (6,31,45,47). On the other hand, the inhibition of the commNTS reduces splanchnic sympathetic nerve activity and, consequently, produces a marked fall in blood pressure in SHR, suggesting this subnucleus of the NTS is tonically active in SHR (41).…”

Section: Discussionmentioning

confidence: 99%

Exercise changes regional vascular control by commissural NTS in spontaneously hypertensive rats

Ogihara

Schoorlemmer

Levada

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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Ogihara CA, Schoorlemmer GHM, Levada AC, Pithon-Curi TC, Curi R, Lopes OU, Colombari E, Sato MA. Exercise changes regional vascular control by commissural NTS in spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol 299: R291-R297, 2010. First published April 21, 2010 doi:10.1152/ajpregu.00055.2009.-Inhibition of the commissural nucleus of the solitary tract (commNTS) induces a fall in sympathetic nerve activity and blood pressure in spontaneously hypertensive rats (SHR), which suggests that this subnucleus of the NTS is a source of sympathoexcitation. Exercise training reduces sympathetic activity and arterial pressure. The purpose of the present study was to investigate whether the swimming exercise can modify the regional vascular responses evoked by inhibition of the commNTS neurons in SHR and normotensive Wistar-Kyoto (WKY) rats. Exercise consisted of swimming, 1 h/day, 5 days/wk for 6 wks, with a load of 2% of the body weight. The day after the last exercise session, the rats were anesthetized with intravenous ␣-chloralose, tracheostomized, and artificially ventilated. The femoral artery was cannulated for mean arterial pressure (MAP) and heart rate recordings, and Doppler flow probes were placed around the lower abdominal aorta and superior mesenteric artery. Microinjection of 50 mM GABA into the commNTS caused similar reductions in MAP in swimming and sedentary SHR (Ϫ25 Ϯ 6 and Ϫ30 Ϯ 5 mmHg, respectively), but hindlimb vascular conductance increased twofold in exercised vs. sedentary SHR (54 Ϯ 8 vs. 24 Ϯ 5%). GABA into the commNTS caused smaller reductions in MAP in swimming and sedentary WKY rats (Ϫ20 Ϯ 4 and Ϫ16 Ϯ 2 mmHg). Hindlimb conductance increased fourfold in exercised vs. sedentary WKY rats (75 Ϯ 2% vs. 19 Ϯ 3%). Therefore, our data suggest that the swimming exercise induced changes in commNTS neurons, as shown by a greater enhancement of hindlimb vasodilatation in WKY vs. SHR rats in response to GABAergic inhibition of these neurons.GABA; cardiovascular; citrate synthase THE NUCLEUS OF THE SOLITARY tract (NTS) is the primary site in the central nervous system that receives the afferents arising from arterial baro-and chemoreceptors (10, 15). The intermediate NTS receives inputs particularly from arterial baroreceptors, but some of these afferents achieve the commNTS (10, 16). The commNTS also receives inputs from arterial chemoreceptors, and seems to be highly sensitive to carotid chemoreceptor stimulation (8, 9, 11).The possible role of the commNTS as a source of sympathoexcitation was first shown by Nelson et al. (33), which demonstrated that nanoliter injections of L-glutamate into the commNTS evoke elevations in heart rate and arterial pressure mediated by the sympathetic nervous system. Electrolytic lesions or chemical inhibition of the commNTS have been shown to markedly decrease the splanchnic sympathetic nerve activity and arterial pressure in spontaneously hypertensive rats (SHR), which suggested that this subnucleus of the NTS contains neurons tonically active in S...

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Section: Discussionmentioning

confidence: 99%

Exercise changes regional vascular control by commissural NTS in spontaneously hypertensive rats

Ogihara

Schoorlemmer

Levada

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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“…13,14 A bipolar stimulating electrode was placed in the NTS using coordinates provided by these authors (0.5 mm caudal to the calamus, 0.5 mm lateral to the midline, and 0.5 mm below the surface of the brain). Using this electrode, an electrolytic lesion was placed in the right NTS to eliminate reflex buffering of responses to drugs injected into the left NTS.…”

Section: Microinjection Experimentsmentioning

confidence: 99%

“…Using the protocol established by Sved and Tsukamoto, 13,14 we lesioned one side of the NTS and microinjected 100 nL of drug into the contralateral NTS. Control injections of artificial cerebrospinal fluid produced inconsistent changes in MAP of Ͻ5 mm Hg in both sham-operated normotensive and hypertensive rats.…”

Section: Microinjection Experimentsmentioning

confidence: 99%

“…Conversely, blockade of GABA B receptors evoked a greater fall in arterial pressure in both models of hypertension compared with normotensive WistarKyoto rats. 14 NTS microinjections of the excitatory amino acid glutamate or drugs that activate or antagonize GABA A receptors produce similar changes in arterial pressure in normotensive and hypertensive rats. All of these data suggest that within the NTS of SHR and DOCA-salt hypertensive rats, there is a tonically enhanced GABA B receptor system.…”

mentioning

confidence: 93%

“…Of note are a series of studies by Sved and colleagues 6,[12][13][14] that demonstrated an enhanced pressor response to activation of GABA B receptors within the NTS in spontaneously hypertensive rat (SHR) 6,[12][13][14] and deoxycorticosterone acetate (DOCA)-salt 14 models of hypertension. Conversely, blockade of GABA B receptors evoked a greater fall in arterial pressure in both models of hypertension compared with normotensive WistarKyoto rats.…”

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Enhanced γ-Aminobutyric Acid–B Receptor Agonist Responses and mRNA Within the Nucleus of the Solitary Tract in Hypertension

1999

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Abstract-␥-Aminobutyric acid-B (GABA B ) receptor function and regulation in the nucleus of the solitary tract (NTS) was examined in Sprague-Dawley rats made chronically (4 to 5 weeks) hypertensive with the one-kidney, figure-8 renal wrap model of hypertension. NTS microinjection of the GABA B agonist baclofen produced a pressor response that was enhanced in hypertensive rats compared with the response observed in sham-operated normotensive rats (36Ϯ4 mm Hg increase in mean arterial pressure in 8 hypertensive rats compared with 21Ϯ2 mm Hg increase in 7 sham-operated normotensive rats, Pϭ0.03). Responses to microinjection of GABA B antagonists (CGP-55845A and SCH-90511), the GABA A agonist muscimol, the GABA A antagonist bicuculline, and the GABA reuptake inhibitor nipecotic acid were not different comparing normotensive sham-operated and hypertensive rats. Renal sympathetic nerve responses to NTS microinjection of these drugs were not different in hypertensive compared with normotensive rats. Micropunches of the NTS were homogenized and reverse transcriptase-polymerase chain reaction was performed to examine mRNA levels for the GABA B receptor. There was a 3-fold increase in GABA B receptor mRNA levels in the caudal NTS of 7 chronically hypertensive rats compared with levels measured in 8 sham-operated normotensive rats (Pϭ0.01). In conclusion, chronic hypertension is associated with an upregulation of GABA B receptor function; however, the tonic activity of the system does not appear to be different between normotensive and hypertensive rats. The upregulation of GABA B receptor function might be due to an increased number of receptors, as suggested by the elevated levels of GABA B receptor mRNA measured in the NTS of hypertensive rats. All of these alterations suggest that hypertension is associated with dynamic changes in receptor-mediated mechanisms within the NTS, and these alterations could modify baroreflex regulation of cardiovascular function in hypertension. Key Words: kidney Ⅲ tractus solitarius Ⅲ hypertension, renal Ⅲ receptors, aminobutyric acid Ⅲ baclofen Ⅲ reverse transcriptase T he nucleus of the solitary tract (NTS) is the brain stem nucleus where baroreceptor afferent fibers make their initial synapse within the central nervous system. Therefore, information regarding the physiology and pharmacology of NTS neurons is critical to our understanding of baroreflex regulation of cardiovascular function. The region of the NTS where baroreceptor afferents terminate contains a high density of both ␥-aminobutyric acid-A (GABA A ) and GABA B receptors. 1,2 A number of in vivo microinjection studies 3-6 as well as in vivo 7-9 and in vitro 10,11 single unit electrophysiological experiments have demonstrated that both GABA A and GABA B receptors play an important role in the integration of baroreceptor afferent inputs and baroreflex function. Since activation of GABA A receptors evokes postsynaptic inhibition and activation of GABA B receptors evokes both presynaptic and postsynaptic inhibition of NTS neuron...

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GABAergic neurons in rat nuclei of solitary tracts receive inhibitory-type synapses from amygdaloid efferents lacking detectable GABA-immunoreactivity

Pickel¹,

Bockstaele²,

Chan³

et al. 1996

J. Neurosci. Res.

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Gamma‐aminobutyric acid (GABA) is a prominent inhibitory transmitter in both the central nucleus of the amygdala (Ce) and the medial nuclei of the solitary tracts (mNTS). These regions are reciprocally connected by anatomical pathways mediating the coordinated visceral responses to emotional stress. To further determine whether GABA is present in the amygdaloid efferents or their targets in the mNTS, we combined peroxidase labeling of Phaseolus vulgaris leucoagglutinin (PHA‐L) or biotinylated dextran amine (BDA) anterogradely transported from the Ce with immunogold‐silver detection of antibodies against GABA in the rat mNTS. By light microscopy, peroxidase labeling for either PHA‐L or BDA was seen in varicose processes, whereas immunogold‐silver labeling for GABA was detected in perikarya and processes throughout the rostrocaudal mNTS. The intermediate mNTS at the level of the area postrema, a region receiving mainly cardiorespiratory and gastric visceral afferents, were examined by electron microscopy. In this region, anterograde labeling was observed exclusively in unmyelinated axons and axon terminals. These terminals lacked detectable GABA‐immunoreactivity, but formed symmetric synapses that are associated with inhibition. The targets of the anterogradely labeled terminals were medium‐sized dendrites both with and without GABA‐labeling. These dendrites often also received convergent input from terminals that were intensely GABA‐immunoreactive. We conclude that visceral activation accompanying emotional response to stress is likely to involve inhibition of GABAergic neurons in the mNTS by non‐GABA‐containing amygdaloid efferents. Furthermore, our results indicate that the inhibition of these GABAergic neurons may be further augmented by release of GABA from other converging terminals in the mNTS. © 1996 Wiley‐Liss, Inc.

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Enhanced gamma-aminobutyric acid-mediated responses in nucleus tractus solitarius of hypertensive rats.

Cited by 55 publications

References 30 publications

Exercise changes regional vascular control by commissural NTS in spontaneously hypertensive rats

Exercise changes regional vascular control by commissural NTS in spontaneously hypertensive rats

Enhanced γ-Aminobutyric Acid–B Receptor Agonist Responses and mRNA Within the Nucleus of the Solitary Tract in Hypertension

GABAergic neurons in rat nuclei of solitary tracts receive inhibitory-type synapses from amygdaloid efferents lacking detectable GABA-immunoreactivity

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