Glutamatergic Inputs in the Hypothalamic Paraventricular Nucleus Maintain Sympathetic Vasomotor Tone in Hypertension

Li, De Pei; Pan, Hui Lin

doi:10.1161/01.hyp.0000259666.99449.74

Cited by 133 publications

(183 citation statements)

References 52 publications

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“…It is possible that the alteration in NMDA mRNA expression in the hypothalamus might be related to the reduced sympathetic activity in FF+A7, and as a consequence, the reduced cardiac sympathetic tone, the improvement on baroreflex control of HR, and the improvement on glucose metabolism observed in these rats. Increased NMDA activity has been related to the higher sympathoexcitation during hypertension 47 or heart failure. 48 Another possibility would be the reduction of the activity of hypothalamic neurons directly related to the energy balance.…”

Section: Discussionmentioning

confidence: 99%

Increasing Angiotensin-(1–7) Levels in the Brain Attenuates Metabolic Syndrome–Related Risks in Fructose-Fed Rats

et al. 2014

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Metabolic syndrome (MetS) is currently recognized as a worldwide health problem, 1,2 and the substantial increase in fructose intake in human diet, especially as high-fructose corn syrup, has been considered a potential factor predisposing humans to MetS. 3,4 MetS is a cluster of different risk factors, such as increase in visceral fat deposition, glucose intolerance, dyslipidemia, and hypertension, which increases the risk of development of cardiovascular and renal diseases and type II diabetes mellitus. 2,5 Recent studies in rodents have shown that the renin-angiotensin system, through the inappropriate overactivity of angiotensin (Ang) II on Ang II type 1 (AT 1 ) receptor especially in the circulation and in the white adipose tissue, plays a pivotal role on the pathogenesis of MetS. [6][7][8] Peripheral blockade of Ang II synthesis or its action on AT 1 receptor attenuates metabolic disorders in obese rodents. [6][7][8] In contrast, the other functional arm of renin-angiotensin system, represented by the actions of Ang-(1-7) on Mas receptor, has been recognized widely as a counter-regulatory axis of Ang II/AT 1 receptor actions.Recent studies have shown that chronic increases in peripheral Ang-(1-7)/Mas receptor activity play a protective role in the regulation of cardiovascular and energy metabolism. Transgenic rats with increased Ang-(1-7) levels in the circulation [TGR(A1-7)3292] are protected against cardiac dysfunction, fibrosis, and hypertension when subjected to deoxycorticosterone (DOCA) acetate-salt model 9 and have enhanced resting glucose and lipid metabolism. 10 Accordingly, Giani et al 11,12 showed that chronic subcutaneous infusion of Ang-(1-7) improved insulin resistance, hypertension, and cardiac remodeling in fructose-fed rats. However, genetic deletion of Mas receptor alters glucose and lipid metabolism and the neural control of blood pressure, inducing a state of MetS. [13][14][15] Taken together, these data provide a clear evidence of a protective role of peripheral Ang-(1-7)/Mas receptor axis in the regulation of cardiovascular system and energy metabolism.Our group showed recently that chronic increase in Ang-(1-7) levels in the brain attenuates DOCA-salt hypertension, and that this effect is related to a dramatic beneficial role Abstract-We evaluated effects of chronic intracerebroventricular infusion of angiotensin (Ang)-(1-7) on cardiovascular and metabolic parameters in fructose-fed (FF) rats. After 6 weeks of fructose intake (10% in drinking water), SpragueDawley rats were subjected to intracerebroventricular infusion of Ang-(1-7) (200 ng/h; FF+A7 group) or 0.9% sterile saline (FF group) for 4 weeks with continued access to fructose. Compared with control rats, FF rats had increased mean arterial pressure and cardiac sympathetic tone with impaired baroreflex sensitivity. FF rats also presented increased circulating triglycerides, leptin, insulin, and glucose with impaired glucose tolerance. Furthermore, relative weights of liver and retroperitoneal adipose tissue were increased...

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Section: Discussionmentioning

confidence: 99%

Increasing Angiotensin-(1–7) Levels in the Brain Attenuates Metabolic Syndrome–Related Risks in Fructose-Fed Rats

et al. 2014

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“…Moreover, reductions of SNA in response to PVN inhibition or blockade of excitatory inputs are more pronounced in water deprived (Freeman and Brooks 2007;Stocker et al 2004b and hypertensive (Allen 2002;Li and Pan 2007) rats. These findings indicate that PVN neuronal activity contributes to both the maintenance of resting SNA and to the elevation of SNA under physiologic and disease conditions.…”

Section: Pvn-rvlm and Pvn-rvlm/iml Neurons And Support Of Sympatheticmentioning

confidence: 98%

“…Over the past several years, studies have increasingly focused on the role of PVN neurons in regulating sympathetic nerve activity (SNA) (Akine et al 2003;Allen 2002;Li and Pan 2007;Li et al 2006;Lovick and Coote 1988b;Porter and Brody 1985;Stern 2004;Toney et al 2003). Early studies showed that stimulation of the PVN reduces visceral organ blood flow and increases arterial blood pressure (ABP) (Martin and Haywood 1992;Porter andBrody 1985, 1986), whereas disinhibition of the PVN by GABA A receptor blockade increases ABP, heart rate, and plasma norepinephrine concentration (Martin and Haywood 1993;Martin et al 1991).…”

Section: Introductionmentioning

confidence: 99%

“…In anesthetized rats, for example, studies have shown that acute inhibition of PVN neuronal activity or blockade of excitatory inputs reduces ongoing renal SNA (RSNA) (Akine et al 2003;Allen 2002;Stocker et al 2004b, lumbar SNA , and ABP (Akine et al 2003;Allen 2002;Freeman and Brooks 2007;Stocker et al 2004b. It is noteworthy that reductions of SNA in response to PVN inhibition are more pronounced in water-deprived (Freeman and Brooks 2007;Stocker et al 2004b and hypertensive (Akine et al 2003;Allen 2002;Li and Pan 2007) rats, suggesting an increased contribution of PVN neuronal activity to the maintenance of resting SNA.…”

Section: Introductionmentioning

confidence: 99%

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In Vivo Discharge Properties of Hypothalamic Paraventricular Nucleus Neurons With Axonal Projections to the Rostral Ventrolateral Medulla

Chen

Toney

2010

Journal of Neurophysiology

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Chen Q-H, Toney GM. In vivo discharge properties of hypothalamic paraventricular nucleus neurons with axonal projections to the rostral ventrolateral medulla. J Neurophysiol 103: 4 -15, 2010. First published November 4, 2009 doi:10.1152/jn.00094.2009. The hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) are key components of a neural network that generates and regulates sympathetic nerve activity (SNA). Although each region has been extensively studied, little is presently known about the in vivo discharge properties of individual PVN neurons that directly innervate the RVLM. Here extracellular recording was performed in anesthetized rats, and antidromic stimulation was used to identify single PVN neurons with axonal projections to the RVLM (n ϭ 94). Neurons were divided into two groups that had either unbranched axons terminating in the RVLM (i.e., PVN-RVLM neurons, n ϭ 65) or collateralized axons targeting both the RVLM and spinal cord [i.e., PVN-RVLM/ intermediolateral cell column (IML) neurons, n ϭ 29]. Many PVN-RVLM (32/65, 49%) and PVN-RVLM/IML (17/29, 59%) neurons were spontaneously active. The average firing frequency was not different across groups. Spike-triggered averaging revealed that spontaneous discharge of most neurons was temporally correlated with renal SNA (PVN-RVLM: 12/21, 57%; PVN-RVLM/IML: 6/9, 67%). Time histograms triggered by the electrocardiogram (ECG) R-wave indicated that discharge of most cells was also cardiac rhythmic (PVN-RVLM: 25/32, 78%; PVN-RVLM/IML: 10/17, 59%). Raising and lowering arterial blood pressure to increase and decrease arterial baroreceptor input caused a corresponding decrease and increase in firing frequency among cells of both groups (PVN-RVLM: 9/13, 69%; PVN-RVLM/IML: 4/4, 100%). These results indicate that PVN-RVLM and PVN-RVLM/IML neurons are both capable of contributing to basal sympathetic activity and its baroreflex modulation.

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“…6 Inhibiting the PVN dramatically reduces sympathetic vasomotor tone, 7 whereas activating the PVN increases sympathetic outflow in SHR. 8 Bilateral electrolytic lesions of the PVN attenuate the sympathetic activity and the development of hypertension in SHR. 9,10 These results indicate the importance of the PVN in the development and progression of hypertension in SHR.…”

Section: Introductionmentioning

confidence: 99%

Artificial microRNA interference targeting AT1a receptors in paraventricular nucleus attenuates hypertension in rats

Zhang

Shi

et al. 2011

Gene Ther

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Excessive sympathetic activity has a crucial role in the initiation and progression of chronic structural alterations in the heart and vessels associated with hypertension. Angiotensin II type 1a receptors (AT 1a R) in paraventricular nucleus (PVN) are involved in sympathetic overdrive and hypertension. The present study was designed to investigate the cardiovascular beneficial effects of the AT 1a R gene silence in the PVN in hypertension. The PVN microinjection of recombinant adenoviral vectors expressing either artificial microRNA (amiRNA) targeting AT 1a receptors (Ad-miR-AT 1a ) or control microRNA (Ad-miR-Con) were carried out in spontaneously hypertensive rats (SHR) and normotensive Wistar rats. The vectors were labels with green fluorescent protein (GFP). The successful amiRNA interference was confirmed by the AT 1 receptors reduction and the GFP expression in the PVN. Significant depressor effects were observed from day 5 to day 20 after Ad-miR-AT 1a treatment in SHR. Ad-miR-AT 1a treatment decreased the ratio of left ventricular weight to body weight, cross-sectional areas of myocytes, myocardial fibrosis, media thickness, and the media/lumen ratio of the aorta and the mesenteric artery in SHR. The amiRNA interference reduced the basal sympathetic activity, cardiac sympathetic afferent reflex, plasma norepinephrine and plasma angiotensin II in SHR. These results indicate that amiRNA interference targeting AT 1a R in the PVN decreases arterial blood pressure, blunts sympathetic activity and improves myocardial and vascular remodeling in SHR.Gene Therapy ( Keywords: RNA interference; AT 1 receptors; hypertension; sympathetic activity; myocardial fibrosis; vascular remodeling INTRODUCTION As a worldwide challenge, hypertension is a powerful independent risk factor for the development of cerebrovascular disease, myocardial infarction, heart failure and peripheral artery disease. Sympathetic overdrive has a key role in the progression of hypertension and related pathological changes. 1,2 Sympathectomy surgery in spontaneously hypertensive rats (SHR) attenuates cardiac fibrosis and hypertension. 3 Central sympathetic deactivation has been considered as an important strategy for arresting hypertension and regressing-related cardiac structural alterations. 4,5 Paraventricular nucleus (PVN) is critical in the integration of sympathetic outflow and cardiovascular activity via its projections to rostral ventrolateral medulla and intermediolateral column of spinal cord. 6 Inhibiting the PVN dramatically reduces sympathetic vasomotor tone, 7 whereas activating the PVN increases sympathetic outflow in SHR. 8 Bilateral electrolytic lesions of the PVN attenuate the sympathetic activity and the development of hypertension in SHR. 9,10 These results indicate the importance of the PVN in the development and progression of hypertension in SHR.It has been found that the angiotensin II type 1 receptors (AT 1 R) in the PVN are increased in SHR 11 and renovascular hypertensive rats. 12 Our recent studies have shown that angio...

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Glutamatergic Inputs in the Hypothalamic Paraventricular Nucleus Maintain Sympathetic Vasomotor Tone in Hypertension

Cited by 133 publications

References 52 publications

Increasing Angiotensin-(1–7) Levels in the Brain Attenuates Metabolic Syndrome–Related Risks in Fructose-Fed Rats

Increasing Angiotensin-(1–7) Levels in the Brain Attenuates Metabolic Syndrome–Related Risks in Fructose-Fed Rats

In Vivo Discharge Properties of Hypothalamic Paraventricular Nucleus Neurons With Axonal Projections to the Rostral Ventrolateral Medulla

Artificial microRNA interference targeting AT1a receptors in paraventricular nucleus attenuates hypertension in rats

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