Tonic Excitatory Input to the Rostral Ventrolateral Medulla in Dahl Salt-Sensitive Rats

Ito, Satoru; Komatsu, Kazutoshi; Tsukamoto, Kazuyoshi; Sved, Alan F.

doi:10.1161/01.hyp.37.2.687

Cited by 70 publications

(75 citation statements)

References 17 publications

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“…Hypertensive rat models with enhanced angiotensinergic activation of the RVLM also appear to have augmented glutamatergic tone (3,19,20). However, in the present study we found no evidence to support the notion that enhanced tonic glutamatergic inputs to the RVLM raise SNA in the OZR.…”

Section: Discussioncontrasting

confidence: 94%

“…Effective antagonism of ionotropic glutamate receptors in the RVLM evoked comparable decreases in SNA, HR, and MAP in OZR and LZR, and this was observed even after the elimination of potentially altered endogenous GABAergic inputs to the RVLM. Unexpectedly, even LZR displayed significant reductions in SNA, HR, and MAP with antagonism of glutamate receptors in the RVLM, in contrast to previous reports of a lack of physiological effects in other normotensive strains (19,20,22). The responses to inhibition of glutamatergic inputs to the RVLM observed in LZR were not likely due to specific conditions of our experiments, because under the same conditions blockade of glutamate receptors in SpragueDawley rats did not alter SNA, HR, or MAP.…”

Section: Discussioncontrasting

confidence: 72%

“…In spontaneously hypertensive rats the tonic CVLM-mediated GABAergic inhibition of the RVLM appears to be attenuated (37). Furthermore, in many hypertensive rat models, tonic activation of RVLM by glutamate and angiotensin II are augmented (9,17,18,19,20). The principle observations of the present study are that 1) inhibition of the RVLM evoked a greater decrease in MAP in OZR compared with LZR; 2) antagonism of AT 1 Fig.…”

Section: Discussionsupporting

confidence: 54%

“…In spontaneously hypertensive rats, Dahl-saltsensitive rats, and renal injury hypertensive rats, the elevated SNA is associated with an increase in the tonic activation of the RVLM by glutamate and angiotensin II (2,9,17,18,19,20). In addition, reduced tonic GABAergic inhibition of the RVLM also appears to contribute to the elevated MAP observed in spontaneously hypertensive rats (38).…”

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confidence: 99%

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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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Section: Discussioncontrasting

confidence: 94%

Section: Discussioncontrasting

confidence: 72%

Section: Discussionsupporting

confidence: 54%

mentioning

confidence: 99%

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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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“…In renovascular hypertensive rats, as well as in SHRs (Ito et al 2000), Dahl salt-sensitive rats (Ito et al 2001) and rats used in an experimental model of pulsatile compression of the RVLM (Morimoto et al 1999), the blockade of excitatory amino acid receptors in the RVLM elicited profound decreases in the arterial pressure. Our hypothesis is that the increased glutamatergic activity in the RVLM seen in hypertension is in part mediated by local or circulating Ang II.…”

Section: The Rostral Ventrolateral Medulla and The Generation Of The mentioning

confidence: 99%

Role of the medulla oblongata in normal and high arterial blood pressure regulation: the contribution of Escola Paulista de Medicina - UNIFESP

Cravo

Campos

Colombari

et al. 2009

An. Acad. Bras. Ciênc.

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Several forms of experimental evidence gathered in the last 37 years have unequivocally established that the medulla oblongata harbors the main neural circuits responsible for generating the vasomotor tone and regulating arterial blood pressure. Our current understanding of this circuitry derives mainly from the studies of Pedro Guertzenstein, a former student who became Professor of Physiology at UNIFESP later, and his colleagues. In this review, we have summarized the main findings as well as our collaboration to a further understanding of the ventrolateral medulla and the control of arterial blood pressure under normal and pathological conditions.

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Altered balance of γ‐aminobutyric acidergic and glutamatergic afferent inputs in rostral ventrolateral medulla‐projecting neurons in the paraventricular nucleus of the hypothalamus of renovascular hypertensive rats

Biancardi

Campos

Stern

2009

J of Comparative Neurology

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An imbalance of excitatory and inhibitory functions has been shown to contribute to numerous pathological disorders. Accumulating evidence supports the idea that a change in hypothalamic γ-aminobutyric acid (GABA)-ergic inhibitory and glutamatergic excitatory synaptic functions contributes to exacerbated neurohumoral drive in prevalent cardiovascular disorders, including hypertension. However, the precise underlying mechanisms and neuronal substrates are still not fully elucidated. In the present study, we combined quantitative immunohistochemistry with neuronal tract tracing to determine whether plastic remodeling of afferent GABAergic and glutamatergic inputs into identified RVLM-projecting neurons of the hypothalamic paraventricular nucleus (PVN-RVLM) contributes to an imbalanced excitatory/inhibitory function in reno-vascular hypertensive rats (RVH). Our results indicate that both GABAergic and glutamatergic innervation densities increased in oxytocin-positive, PVN-RVLM (OT-PVN-RVLM) neurons in RVH rats. Despite this concomitant increase, time-dependent and compartment-specific differences in the reorganization of these inputs resulted in an altered balance of excitatory/inhibitory inputs in somatic and dendritic compartments. A net predominance of excitatory over inhibitory inputs was found in OT-PVN-RVLM proximal dendrites. Our results indicate that, along with previously described changes in neurotransmitter release probability and postsynaptic receptor function, remodeling of GABAergic and glutamatergic afferent inputs contributes as an underlying mechanism to the altered excitatory/ inhibitory balance in the PVN of hypertensive rats.

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Tonic Excitatory Input to the Rostral Ventrolateral Medulla in Dahl Salt-Sensitive Rats

Cited by 70 publications

References 17 publications

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

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

Role of the medulla oblongata in normal and high arterial blood pressure regulation: the contribution of Escola Paulista de Medicina - UNIFESP

Altered balance of γ‐aminobutyric acidergic and glutamatergic afferent inputs in rostral ventrolateral medulla‐projecting neurons in the paraventricular nucleus of the hypothalamus of renovascular hypertensive rats

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