Abstract-Increased dietary salt exaggerates arterial blood pressure (ABP) responses evoked from the rostral ventrolateral medulla (RVLM). The present study determined whether these enhanced pressor responses were directly attributable to a greater increase in sympathetic nerve activity (SNA) and whether these enhanced responses were balanced by a greater responsiveness of RVLM neurons to inhibitory input. Male Sprague-Dawley rats were fed normal chow and given access to either water or a 1% NaCl solution for 14 days. Injection of L-glutamate (0.03, 0.1, 1.0, and 3.0 nmol) into the RVLM produced a significantly greater increase in renal SNA, splanchnic SNA, and ABP in rats drinking 1% NaCl versus water. Conversely, injection of the inhibitory amino acid ␥-aminobutyric acid (0.1, 1.0, and 10 nmol) into the RVLM produced significantly greater decreases in renal SNA, splanchnic SNA, and ABP of rats drinking 1% NaCl versus water. These enhanced SNA and ABP responses to L-glutamate and ␥-aminobutyric acid were not observed in rats drinking 1% NaCl for 1 or 7 days but were present in rats drinking 1% NaCl for 21 days. Moreover, the dietary salt-induced enhancement of both sympathoexcitatory and sympathoinhibitory responses from the RVLM persisted after the 1% NaCl solution was replaced with water for 1, but not 7, days. These findings indicate that the potentiated ABP responses observed previously are mediated by parallel changes in SNA, and these responses depend on a slowly developing and reversible form of neuronal plasticity. Key Words: sympathetic nervous system Ⅲ blood pressure Ⅲ glutamate Ⅲ GABA Ⅲ sodium chloride E levated dietary salt intake is a contributing factor to the pathogenesis of hypertension in both humans and experimental animal models. 1-4 Elevated dietary salt does not invariably increase arterial blood pressure (ABP) but does contribute to the development of arterial hypertension or exaggerate the severity of hypertension in salt-sensitive individuals and experimental models. Several mechanisms have been proposed to explain the salt sensitivity of ABP, including increased water and sodium retention with resultant expansion of blood volume or a neurogenically mediated increase in total peripheral resistance. 1,3,4 The hypothesis that elevated dietary salt increases ABP through neurogenic mechanisms arises from several lines of evidence. First, salt-sensitive hypertension in both humans and experimental models is associated with elevations in sympathetic nerve activity (SNA). 4 Second, Pawloski-Dahm and Gordon 5 reported that excitation of neurons in the rostral ventrolateral medulla (RVLM) with microinjection of L-glutamate produced significantly larger increases in ABP of rats drinking 0.9% NaCl versus those drinking water for 14 days. The RVLM contains bulbospinal neurons that provide the major excitatory drive to sympathetic preganglionic vasomotor neurons in the thoracic and lumbar segments of the spinal cord. 6,7 Moreover, elevated dietary salt enhanced the pressor response to several other di...
Abstract-Activation of the sympathetic nervous system contributes to the pathogenesis of obesity-induced hypertension.The present study sought to determine whether sympathetic regulatory neurons of the rostral ventrolateral medulla contribute to the elevated blood pressure in obese rats. Male Sprague-Dawley rats (350 to 425 g) were placed on a moderately high-fat diet (32% kcal as fat) or a low-fat (LF) diet (10.6% kcal as fat). After 13 weeks, rats fed the moderately high-fat diet segregated into obesity-prone (OP) and obesity- Key Words: obesity Ⅲ sympathetic Ⅲ blood pressure R isk estimates from the Farmington Heart Study suggest that Ϸ78% of essential hypertension in men and 65% in women can be directly attributed to obesity. 1 Several lines of evidence strongly indicate that activation of the sympathetic nervous system contributes to the etiology of obesity-induced hypertension. 2,3 First, renal norepinephrine spillover is approximately doubled in obese versus lean subjects. 4 -6 Second, muscle sympathetic nerve activity assessed by microneurography is higher in obese humans. 7,8 Consistent with this notion, pharmacological blockade of peripheral adrenergic receptors 9 or ganglionic blockade 10 reduces arterial blood pressure (ABP) to a greater extent in obese versus lean subjects. Similar observations have been reported in animal models of obesity hypertension. [11][12][13][14][15][16] For example, bilateral renal denervation prevents the development of obesityinduced hypertension in dogs. 13 Despite the importance of sympathetic nervous system activation in obesity-induced hypertension, the central neural mechanisms and pathways that support the elevated sympathetic outflow and ABP are poorly understood.Basal sympathetic outflow arises from the tonic drive of neurons in the rostral ventrolateral medulla (RVLM) to preganglionic neurons in the thoracic and lumbar spinal cord. 17 Although other hypothalamic and pontomedullary structures innervate sympathetic preganglionic neurons, 17 and stimulation of these regions can increase sympathetic outflow and ABP through pathways independent of the RVLM, 18,19 the RVLM is regarded as the major vasomotor center within the central nervous system. 17 For example, a myriad of studies indicate that RVLM neurons mediate numerous reflexive adjustments in sympathetic outflow under physiological conditions. 17 Electrical stimulation or chemical excitation of this region profoundly increases sympathetic nerve activity and ABP. 17 Moreover, several studies have suggested that RVLM neurons contribute to the elevated sympathetic outflow and ABP in several experimental animal models of hypertension. 20 -24 Interestingly, Lohmeier et al 25 reported an increased level of Fos expression, a marker of synaptic activation, in the RVLM of obese hypertensive dogs.The purpose of the present study was to determine whether RVLM neurons contribute to the elevated ABP in obesityinduced hypertension. Previous studies have demonstrated that feeding rats a moderate high-fat diet for an extended...
Abstract-Excess dietary salt intake contributes to or exacerbates some forms of hypertension by increasing sympathetic nerve activity (SNA) and arterial blood pressure (ABP) through angiotensin II (Ang II) type 1 receptor activation in the rostral ventrolateral medulla (RVLM). Despite this interaction among dietary salt, Ang II, and the RVLM, no studies have directly examined whether dietary salt by itself alters Ang II-dependent responses and regulation of RVLM neurons, SNA, and ABP. Therefore, the present study directly tested this hypothesis. Male Sprague-Dawley rats were fed normal chow and given access to water or 0.9% NaCl solution for 14 days. Key Words: sympathetic nervous system Ⅲ blood pressure Ⅲ hypertension Ⅲ brain Ⅲ sodium T he brain renin-angiotensin system plays an important role in cardiovascular regulation through its ability to modulate sympathetic nerve activity (SNA) and arterial blood pressure (ABP). One of the major centers postulated to mediate the sympathoexcitatory actions of brain angiotensin II (Ang II) is the rostral ventrolateral medulla (RVLM). 1,2 The RVLM contains tonically active, bulbospinal neurons that mediate a number of sympathetically mediated reflexes and contribute to sympathoexcitatory disease states. 3 The RVLM contains a high density of Ang II type 1 (AT 1 ) receptors, 1 and microinjection of Ang II into the RVLM produces an AT 1 receptor-mediated increase in SNA and ABP. 2 Overexpression of constitutively active AT 1 a receptors in the RVLM increases ABP, 4 and blockade of RVLM AT 1 receptors has been reported to reduce ABP in several forms of experimental hypertension 5,6 and other sympathoexcitatory conditions. 7,8 A major factor that contributes to the pathogenesis of hypertension and modulates the excitability of RVLM sympathetic-regulatory neurons is dietary salt intake. Evidence from both clinical and experimental models indicate that excess dietary salt intake exacerbates the level of hypertension, including Ang II-dependent models, via increases in sympathetic vasomotor tone. 9,10 In several instances, findings from experimental models suggest that the elevated sympathetic tone depends on altered neurotransmission and AT 1 receptor activation in the RVLM. 5,6 However, few studies have directly examined whether excess dietary salt intake by itself affects the regulation of RVLM sympathetic-regulatory neurons. To date, the limited data indicate that elevated dietary salt intake enhances both sympathoexcitatory and sympathoinhibitory responses evoked by a number of neurotransmitters exogenously applied to the RVLM. [11][12][13] However, these enhanced responses could not be attributed to changes in downstream sympathetic pathways 13,14 or vascular reactivity. 12,13,15 Despite the ability of dietary salt intake to modulate the excitability of RVLM neurons and the role of RVLM AT 1 receptors in salt-dependent hypertension, no studies have determined whether dietary salt intake by itself alters Ang II-dependent responses or regulation of RVLM neurons, SNA, and ABP. ...
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