Role of rostral ventrolateral medulla in centrally mediated pressor responses

Kiely, James M.; Gordon, Frank J.

doi:10.1152/ajpheart.1994.267.4.h1549

Cited by 84 publications

(83 citation statements)

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“…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: 71%

“…To confirm the blockade of ionotropic glutamate receptors in RVLM, stimulation of the right sciatic nerve (10 s of 1-ms pulses at 20 Hz and 300 A) was performed. These stimulation parameters produce reliable rises in SNA and MAP that are eliminated or reversed after antagonism of ionotropic glutamate receptors in the RVLM (22). All rats included in the study showed the expected responses before brain stem microinjections and an absence of responses after microinjections of kynurenate into the RVLM (see Fig.…”

Section: Methodsmentioning

confidence: 89%

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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: 71%

Section: Methodsmentioning

confidence: 89%

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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“…The pattern of cardiovascular adjustments observed in the present study is also compatible with previously described data (Kiely and Gordon 1994, Yardley and Hilton 1987, Hilton and Zbrozyna 1963. This pattern is characterized by increases in arterial blood pressure and heart rate.…”

Section: Nitric Oxide Release In Defense Reactionsupporting

confidence: 93%

Evidence for a role of nitric oxide in hindlimb vasodilation induced by hypothalamic stimulation in anesthetized rats

Ferreira-Neto

Possas

Lopes

et al. 2005

An. Acad. Bras. Ciênc.

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Electrical stimulation of the hypothalamus produces cardiovascular adjustments consisting of hypertension, tachycardia, visceral vasoconstriction and hindlimb vasodilation. Previous studies have demonstrated that hindlimb vasodilation is due a reduction of sympathetic vasoconstrictor tone and to activation of β 2 -adrenergic receptors by catecholamine release. However, the existence of a yet unidentified vasodilator mechanism has also been proposed. Recent studies have suggested that nitric oxide (NO) may be involved. The aim of the present study was to investigate the role of NO in the hindquarter vasodilation in response to hypothalamic stimulation. In pentobarbital-anesthetized rats hypothalamic stimulation (100 Hz, 150µA, 6 s) produced hypertension, tachycardia, hindquarter vasodilation and mesenteric vasoconstriction. Alpha-adrenoceptor blockade with phentolamine (1.5 mg/kg, iv) plus bilateral adrenalectomy did not modify hypertension, tachycardia or mesenteric vasoconstriction induced by hypothalamic stimulation. Hindquarter vasodilation was strongly reduced but not abolished. The remaining vasodilation was completely abolished after iv injection of the NOS inhibitor L-NAME (20 mg/kg, iv). To properly evaluate the role of the mechanism of NO in hindquarter vasodilation, in a second group of animals L-NAME was administered before α-adrenoceptor blockade plus adrenalectomy. L-NAME treatment strongly reduced hindquarter vasodilation in magnitude and duration. These results suggest that NO is involved in the hindquarter vasodilation produced by hypothalamic stimulation.

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“…18 As mentioned above, injection of muscimol into the ipsilateral RVLM attenuated the pressor and sympathoexcitatory response evoked from the PVN by approximately one half. The dose of muscimol injected (1 nmol) was 10 times greater than that which has previously been shown to result in a profound fall in arterial pressure when injected bilaterally into the RVLM, 9 indicating that it was sufficient to produce complete or nearly complete inhibition of RVLM neurons. Thus, the fact that the pressor and sympathoexcitatory response evoked from the PVN was reduced but not abolished after injection of muscimol into the ipsilateral RVLM supports the finding of Kiely and Gordon 9 that this response is mediated partly by a descending pathway that includes a synapse within the RVLM and partly by a separate descending pathway that is independent of the RVLM.…”

Section: Tagawa and Dampney Function Of At 1 Receptors On Rvlm Pressomentioning

confidence: 78%

“…6 Although glutamate receptors have been shown to mediate excitatory synaptic inputs to RVLM sympathoexcitatory neurons that are activated by stimulation of a variety of peripheral receptors and some supramedullary regions, 1,2,7,8 there is also evidence that excitatory inputs to these neurons activated by stimulation of certain hypothalamic regions (eg, the paraventricular nucleus [PVN] and perifornical area) are nonglutamatergic. 9 This raises the possibility that AT 1 receptors in the RVLM may mediate excitatory inputs to RVLM neurons originating from these hypothalamic regions. To test this hypothesis, in the present study, we have determined the effect of specific blockade of AT 1 receptors in the RVLM on the excitation of RVLM sympathoexcitatory neurons evoked by activation of the hypothalamic PVN.…”

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confidence: 99%

AT ₁ Receptors Mediate Excitatory Inputs to Rostral Ventrolateral Medulla Pressor Neurons From Hypothalamus

1999

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Abstract-Angiotensin II type 1 (AT 1 ) receptors are located on pressor neurons in the rostral ventrolateral medulla, and their activation results in an increase in arterial pressure. However, the normal role of these AT 1 receptors in cardiovascular regulation is unknown. In this study, we tested the hypothesis that these receptors mediate synaptic excitation of rostral ventrolateral medullary pressor neurons in response to activation of the hypothalamic paraventricular nucleus. In anesthetized rats, microinjections of the ␥-aminobutyric acid receptor antagonist bicuculline were made into the paraventricular nucleus; this injection causes activation of the nucleus as a consequence of disinhibition. The pressor and sympathoexcitatory responses evoked by paraventricular nucleus activation were significantly reduced (by Ϸ40% to 50%) after microinjection of the specific AT 1 receptor antagonists losartan or L-158,809 into the rostral ventrolateral medulla on the ipsilateral, but not contralateral, side. These responses were reduced to a similar degree after microinjections of the neuroinhibitory compound muscimol into the ipsilateral, but not contralateral, rostral ventrolateral medulla. However, bilateral microinjections of the glutamate receptor antagonist kynurenic acid into the rostral ventrolateral medulla had no effect on the responses evoked from the paraventricular nucleus. Conversely, bilateral microinjections of kynurenic acid into the rostral ventrolateral medulla virtually abolished the somatosympathoexcitatory reflex, whereas bilateral microinjections of losartan or L-158,809 had no effect on this reflex. The results indicate that excitatory synaptic inputs to pressor neurons in the rostral ventrolateral medulla arising from activation of the paraventricular nucleus are mediated predominantly by AT 1 receptors. (Hypertension. 1999;34:1301-1307.)Key Words: angiotensin II Ⅲ blood pressure Ⅲ brain Ⅲ receptors, glutamate Ⅲ bicuculline Ⅲ blood vessels I t is well established that the rostral part of the ventrolateral medulla (RVLM) contains a group of spinally projecting sympathoexcitatory neurons that play a crucial role in the tonic and phasic regulation of sympathetic vasomotor activity and arterial blood pressure (for reviews see References 1 and 2). These neurons are a site of convergence of central pathways subserving many cardiovascular reflexes as well as responses evoked from higher brain regions. 1,2 Numerous studies have demonstrated that glutamate and ␥-aminobutyric acid (GABA) receptors play a major role in the synaptic regulation of RVLM sympathoexcitatory neurons. 1,2 There is also evidence, however, indicating that angiotensin (Ang) receptors may also play a role in the synaptic regulation of these neurons. First, studies using in vitro autoradiography have shown that there is a high density of Ang receptors in the RVLM of several mammalian species, including humans (for review see Reference 3). These receptors are predominantly Ang II type 1 (AT 1 ) receptors, and their location corresponds...

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Role of rostral ventrolateral medulla in centrally mediated pressor responses

Cited by 84 publications

References 0 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

Evidence for a role of nitric oxide in hindlimb vasodilation induced by hypothalamic stimulation in anesthetized rats

AT ₁ Receptors Mediate Excitatory Inputs to Rostral Ventrolateral Medulla Pressor Neurons From Hypothalamus

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Role of rostral ventrolateral medulla in centrally mediated pressor responses

Cited by 84 publications

References 0 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

Evidence for a role of nitric oxide in hindlimb vasodilation induced by hypothalamic stimulation in anesthetized rats

AT 1 Receptors Mediate Excitatory Inputs to Rostral Ventrolateral Medulla Pressor Neurons From Hypothalamus

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AT ₁ Receptors Mediate Excitatory Inputs to Rostral Ventrolateral Medulla Pressor Neurons From Hypothalamus