Increased Dietary Salt Enhances Sympathoexcitatory and Sympathoinhibitory Responses From the Rostral Ventrolateral Medulla

Adams, Julye M; Madden, Christopher J.; Sved, Alan F.; Stocker, Sean D.

doi:10.1161/hypertensionaha.107.091843

Cited by 78 publications

(96 citation statements)

References 25 publications

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“…62 Increasing evidence suggests that central nervous system mechanisms are involved in salt-induced hypertension, although the kidney also has a key role in salt-induced hypertension. [63][64][65][66] We sought to determine whether high salt intake increases hypertension in the SHR and whether the increased ROS production in the RVLM contributes to this mechanism. 18 High salt intake augmented the development of hypertension in the SHR beginning at the age of 6-12 weeks.…”

Section: Influence Of Salt and Obesity On Oxidative Stress In The Bramentioning

confidence: 99%

Oxidative stress in the cardiovascular center has a pivotal role in the sympathetic activation in hypertension

Hirooka

2011

Hypertens Res

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Oxidative stress in the cardiovascular center has a pivotal role in the sympathetic activation in hypertension Yoshitaka HirookaActivation of the sympathetic nervous system has an important role in the pathogenesis of hypertension. However, the precise mechanisms involved are not fully understood. Oxidative stress may be important in hypertension as well as in other cardiovascular disorders. We investigated the role of oxidative stress, particularly in the rostral ventrolateral medulla (RVLM), which is known as the cardiovascular center in the brainstem, in the activation of the sympathetic nervous system in hypertension. We observed that the reactive oxygen species (ROS) production increases in the RVLM in hypertensive rats, thereby enhancing the central sympathetic outflow, which leads to hypertension. Furthermore, the environmental factors of high salt intake and a high-calorie diet may also increase the ROS production in the RVLM, thereby activating the central sympathetic outflow and increasing the risk of hypertension. The activation of the nicotinamide adenine dinucleotide phosphate oxidase via the angiotensin type 1 (AT1) receptors is suggested to be the major source of ROS production, and an altered downstream signaling pathway is involved in the activation of the RVLM neurons, leading to enhanced central sympathetic outflow and hypertension. Thus, the brain AT1 receptors may be novel therapeutic targets, and, in fact, oral treatment with angiotensin receptor blockers has been found to inhibit the central AT1 receptors, despite the blood-brain barrier.

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Section: Influence Of Salt and Obesity On Oxidative Stress In The Bramentioning

confidence: 99%

Oxidative stress in the cardiovascular center has a pivotal role in the sympathetic activation in hypertension

Hirooka

2011

Hypertens Res

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“…These spinally projecting RVLM neurons are regulated by the major inhibitory and excitatory neurotransmitters GABA and glutamate, respectively (19,43). Microinjection of glutamate and glutamate receptor agonists into the RVLM results in large increases in sympathetic nerve activity and blood pressure (1, 18,39,52,60,62). Our laboratory and others have shown that sedentary vs. active rats exhibit greater indexes of sympathoexcitation when RVLM neurons are activated with glutamate (41, 50).…”

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(In)activity-dependent alterations in resting and reflex control of splanchnic sympathetic nerve activity

Mischel

Mueller

2011

Journal of Applied Physiology

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Mischel NA, Mueller PJ. (In)activity-dependent alterations in resting and reflex control of splanchnic sympathetic nerve activity. J Appl Physiol 111: 1854 -1862. First published October 6, 2011 doi:10.1152/japplphysiol.00961.2011The negative effects of sympathetic overactivity on long-term cardiovascular health are becoming increasingly clear. Moreover, recent work done in animal models of cardiovascular disease suggests that sympathetic tone to the splanchnic vasculature may play an important role in the development and maintenance of these disease states. Work from our laboratory and others led us to hypothesize that a lack of chronic physical activity increases resting and reflex-mediated splanchnic sympathetic nerve activity, possibly through changes occurring in a key brain stem center involved in sympathetic regulation, the rostral ventrolateral medulla (RVLM). To address this hypothesis, we recorded mean arterial pressure (MAP) and splanchnic sympathetic nerve activity (SSNA) in a group of active and sedentary animals that had been housed for 10 -13 wk with or without running wheels, respectively. In experiments performed under Inactin anesthesia, we tested responses to RVLM microinjections of glutamate, responses to baroreceptor unloading, and vascular reactivity, the latter of which was performed under conditions of autonomic blockade. Sedentary animals exhibited enhanced resting SSNA and MAP, augmented increases in SSNA to RVLM activation and baroreceptor unloading, and enhanced vascular reactivity to ␣ 1-receptor mediated vasoconstriction. Our results suggest that a sedentary lifestyle increases the risk of cardiovascular disease by augmenting resting and reflex-mediated sympathetic output to the splanchnic circulation and also by increasing vascular sensitivity to adrenergic stimulation. We speculate that regular physical exercise offsets or reverses the progression of these disease processes via similar or disparate mechanisms and warrant further examination into physical (in)activity-induced sympathetic nervous system plasticity. sympathetic nervous system; sedentary lifestyle; blood pressure CARDIOVASCULAR DISEASE is currently the leading cause of death in the United States and has an economic impact in the hundreds of billions of dollars (35,58). One of the primary risk factors for cardiovascular disease is a lack of regular exercise (35). The detrimental effects of a sedentary lifestyle on cardiovascular health have been studied and documented for over 50 yr (2,11,48). However, only recently have many conditions linked to physical inactivity, such as the metabolic syndrome, heart failure, and hypertension, been associated with overactivity of the sympathetic nervous system (7,13,14,22,29,63,68). Since sympathetic overactivity can have deleterious effects on the cardiovascular system both directly and indirectly (16,17), it is important to study the mechanisms by which physical inactivity can raise sympathetic output and negatively impact the cardiovascular system. Sympathetic activity is gener...

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“…At the central level, there is evidence that a high-salt diet may alter input/output signals in the medulla, including the NTS. For example, increased dietary salt was shown to alter the balance of sympathoexcitatory and sympathoinhibitory responses from/to the rostral ventrolateral medulla, while high sodium enhanced activation of neurons in the NTS and the rostral ventrolateral medulla, accounting for the observed decreased baroreflex (13,14).…”

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Aldosterone-Sensitive Nucleus Tractus Solitarius Neurons Regulate Sensitivity of the Baroreceptor Reflex in High Sodium–Loaded Rats

Masuda¹,

Hirabara²,

Nakamura³

et al. 2010

J Pharmacol Sci

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Baroreceptor and chemoreceptor signals are transmitted to the nucleus tractus solitarius (NTS) via the primary afferent fibers of the glossopharyngeal and vagal nerves, suggesting a role for the NTS in modulating the arterial baroreceptor reflex (baroreflex). The NTS contains numerous neurotransmitters and receptors, including glutamate, GABA, or substance P (1). However, the role of these neurotransmitters in regulatory baroreceptor and chemoreceptor signals is not fully understood. Recently, the enzyme 11β-hydroxysteroid dehydrogenase type 2 (HSD2) and the mineralocorticoid receptors (MR) were identified in the NTS along with common neurotransmitters; such neurons are termed 'aldosterone-sensitive HSD2 neurons' (2 -5). Furthermore, a number of studies have shown that the aldosterone-sensitive HSD2 neurons in the NTS are involved in sodium appetite or in regulation of body fluid circulation as they are selectively activated by sodium deficiency (2, 4).Aldosterone is secreted from the adrenal cortex in response to sodium deficiency and also amplifies sodium intake. A cardiovascular role for aldosterone has been suggested from the evidence of MR expression in vascular tissues, including the heart. Furthermore, some studies have reported a role for aldosterone in the baroreflex response. For example, both acute and chronic peripheral aldosterone administration impaired baroreceptor responses in dogs (6) and in humans (7). In addition, central infusion of sodium-enriched artificial cerebrospinal fluid (aCSF) caused increased aldosterone and corticosterone levels in the hypothalamus and impaired baroreceptor function (8, 9), suggesting a role for central aldosterone in baroreflex function. However, the role of aldosteronesensitive neurons in the NTS in baroreflex responses remains unclear.In the present study, we tested the hypothesis that the aldosterone-sensitive neurons in the NTS regulate the baroreflex function. To address this hypothesis, we examined the baroreflex sensitivity induced by phenylephrine in high sodium-loaded rats.Male Wistar rats (180 -200 g) were purchased from Kyudo (Kumamoto). The animals were maintained at 24 ± 2°C with a 12-h light-dark cycle (light on at 07:00 Medicine, Kyoto 602-8566, Japan Received December 25, 2009; Accepted February 19, 2010 Abstract. We examined the role of aldosterone-sensitive neurons in the nucleus tractus solitarius (NTS) in the arterial baroreceptor reflex (baroreflex) function. Baroreflex sensitivity was induced by phenylephrine in high sodium-loaded rats and was significantly reduced. This baroreflex sensitivity was reversed by microinjection of the mineralocorticoid receptor (MR) antagonist eplerenone into the NTS. 11β-Hydroxysteroid dehydrogenase type 2 neurons and MR were also identified in the NTS. These data suggest that the aldosterone-sensitive neurons in the NTS may have an important role in baroreflex function.

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Increased Dietary Salt Enhances Sympathoexcitatory and Sympathoinhibitory Responses From the Rostral Ventrolateral Medulla

Cited by 78 publications

References 25 publications

Oxidative stress in the cardiovascular center has a pivotal role in the sympathetic activation in hypertension

Oxidative stress in the cardiovascular center has a pivotal role in the sympathetic activation in hypertension

(In)activity-dependent alterations in resting and reflex control of splanchnic sympathetic nerve activity

Aldosterone-Sensitive Nucleus Tractus Solitarius Neurons Regulate Sensitivity of the Baroreceptor Reflex in High Sodium–Loaded Rats

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