Chronic Hypertension Enhances the Postsynaptic Effect of Baclofen in the Nucleus Tractus Solitarius

Zhang, Weirong; Herrera-Rosales, Myrna; Mifflin, Steve

doi:10.1161/01.hyp.0000253091.82501.c0

Cited by 17 publications

(29 citation statements)

References 23 publications

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“…Metabotropic receptor-mediated responses do not typically survive enzymatic treatment; therefore, GABA B receptors have been studied in a hindbrain slice preparation. The current observed during activation of GABA B receptors is larger in NTS neurons recorded in slices obtained from hypertensive compared with normotensive rats [4].…”

Section: Nucleus Of the Solitary Tractmentioning

confidence: 82%

New insights into the electrophysiology of brainstem circuits controlling blood pressure

Mifflin¹

2007

Current Science Inc

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The brainstem contains the necessary circuitry for the maintenance and regulation of arterial blood pressure. It has become increasingly clear in the past few years that the characteristics of the neurons that constitute these circuits are not static, but can be altered in the face of chronic changes in physiological state. Alterations in voltage-gated and ligand-gated ion channels have been reported in neurons located within the nucleus of the solitary tract and the nucleus ambiguus in response to hypertension and exposures to hypoxia and environmental pollutants (eg, ozone and cigarette smoke). A discussion of these neuronal adaptations, the mechanisms that might initiate and sustain the adaptations, and their potential significance is the focus of this brief review.

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Section: Nucleus Of the Solitary Tractmentioning

confidence: 82%

New insights into the electrophysiology of brainstem circuits controlling blood pressure

Mifflin¹

2007

Current Science Inc

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“…In a renal wrap hypertensive rat model, increased basal MAP is accompanied by altered processing of baroreceptor inputs at the NTS (47). Augmented inputs from excitatory baroreceptor afferent nerves are met with enhanced presynaptic GABAergic inhibition of glutamate release from baroreceptor afferent terminals combined with a postsynaptic GABA B receptor-mediated reduction in the excitability of NTS neurons receiving baroreceptor inputs (46,48). Whether chronically elevated baroreceptor afferent activity in the OZR is associated with changes in the processing of incoming sensory information at the NTS warrants further study.…”

Section: Discussionmentioning

confidence: 99%

Altered regulation of the rostral ventrolateral medulla in hypertensive obese Zucker rats

Huber

Schreihofer

2011

American Journal of Physiology-Heart and Circulatory Physiology

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rats (OZR) have elevated sympathetic nerve activity (SNA) and mean arterial pressure (MAP) compared with lean Zucker rats (LZR). We examined whether altered tonic glutamatergic, angiotensinergic, or GABAergic inputs to the rostral ventrolateral medulla (RVLM) contribute to elevated SNA and MAP in OZR. Male rats (14 -18 wk) were anesthetized with urethane (1.5 g/kg iv), ventilated, and paralyzed to record splanchnic SNA, heart rate (HR), and MAP. Inhibition of the RVLM by microinjections of muscimol eliminated SNA and evoked greater decreases in MAP in OZR vs. LZR (P Ͻ 0.05). Antagonism of angiotensin AT 1 receptors in RVLM with losartan yielded modest decreases in SNA and MAP in OZR but not LZR (P Ͻ 0.05). However, antagonism of ionotropic glutamate receptors in RVLM with kynurenate produced comparable decreases in SNA, HR, and MAP in OZR and LZR. Antagonism of GABA A receptors in RVLM with gabazine evoked smaller rises in SNA, HR, and MAP in OZR vs. LZR (P Ͻ 0.05), whereas responses to microinjections of GABA into RVLM were comparable. Inhibition of the caudal ventrolateral medulla, a major source of GABA to the RVLM, evoked attenuated rises in SNA and HR in OZR (P Ͻ0.05). Likewise, inhibition of nucleus tractus solitarius, the major excitatory input to caudal ventrolateral medulla, produced smaller rises in SNA and HR in OZR. These results suggest the elevated SNA and MAP in OZR is derived from the RVLM and that enhanced angiotensinergic activation and reduced GABAergic inhibition of the RVLM may contribute to the elevated SNA and MAP in the OZR.hypertension; sympathetic nerve activity; muscimol; kynurenate; gabazine; losartan ACCUMULATION OF EXCESS BODY fat is an independent risk factor for elevated mean arterial pressure (MAP; Refs. 8, 13, 26). Over activation of sympathetic nerves that regulate MAP is a hallmark of obesity-induced hypertension (8, 11). Obese hypertensive human subjects have increased muscle sympathetic nerve activity (SNA) characterized by a recruitment of previously silent sympathetic fibers (24). Some obese hypertensives present with elevated plasma levels of catecholamines (26), whereas others report increases in norepinephrine spillover only to selective targets such as the kidney (30). Nevertheless, acute elimination of SNA evokes larger decreases in MAP in obese subjects compared with gender and age-matched lean subjects (36), suggesting an enhanced sympathetic contribution to the maintenance of MAP with obesity-related hypertension.Rat models of obesity mimic the enhanced sympathetic vasomotor tone observed in obese humans. In adult obese Zucker rats (OZR), renal and splanchnic SNA and MAP are elevated (16, 27) compared with age-matched lean Zucker rats (LZR). Furthermore, autonomic ganglionic blockade evokes a larger decrease in basal MAP in OZR than in LZR (31). Similarly, elimination of sympathetic vasomotor tone by inhibition of rostral ventrolateral medulla (RVLM), the primary source of drive for SNA, evokes a greater decrease in MAP in Sprague-Dawley rats made obese by a high-f...

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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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Chronic Hypertension Enhances the Postsynaptic Effect of Baclofen in the Nucleus Tractus Solitarius

Cited by 17 publications

References 23 publications

New insights into the electrophysiology of brainstem circuits controlling blood pressure

New insights into the electrophysiology of brainstem circuits controlling blood pressure

Altered regulation of the rostral ventrolateral medulla in hypertensive obese Zucker rats

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

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