scholarly journals Water deprivation increases respiratory rhythmic sympathetic discharge through a mechanism that depends on neuronal activity in the hypothalamic paraventricular nucleus (PVN)

2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Walter Holbein ◽  
Alfredo S Calderon ◽  
Mary Ann Andrade ◽  
Myrna Herrera‐Rosales ◽  
Glenn M Toney
2013 ◽  
Vol 305 (12) ◽  
pp. H1772-H1780 ◽  
Author(s):  
Amanda L. Sharpe ◽  
Alfredo S. Calderon ◽  
Mary Ann Andrade ◽  
J. Thomas Cunningham ◽  
Steven W. Mifflin ◽  
...  

Like humans with sleep apnea, rats exposed to chronic intermittent hypoxia (CIH) experience arterial hypoxemias and develop hypertension characterized by exaggerated sympathetic nerve activity (SNA). To gain insights into the poorly understood mechanisms that initiate sleep apnea/CIH-associated hypertension, experiments were performed in rats exposed to CIH for only 7 days. Compared with sham-treated normoxic control rats, CIH-exposed rats ( n = 8 rats/group) had significantly increased hematocrit ( P < 0.001) and mean arterial pressure (MAP; P < 0.05). Blockade of ganglionic transmission caused a significantly ( P < 0.05) greater reduction of MAP in rats exposed to CIH than control rats ( n = 8 rats/group), indicating a greater contribution of SNA in the support of MAP even at this early stage of CIH hypertension. Chemical inhibition of neuronal discharge in the hypothalamic paraventricular nucleus (PVN) (100 pmol muscimol) had no effect on renal SNA but reduced lumbar SNA ( P < 0.005) and MAP ( P < 0.05) more in CIH-exposed rats ( n = 8) than control rats ( n = 7), indicating that CIH increased the contribution of PVN neuronal activity in the support of lumbar SNA and MAP. Because CIH activates brain regions controlling body fluid homeostasis, the effects of internal carotid artery injection of hypertonic saline were tested and determined to increase lumbar SNA more ( P < 0.05) in CIH-exposed rats than in control rats ( n = 9 rats/group). We conclude that neurogenic mechanisms are activated early in the development of CIH hypertension such that elevated MAP relies on increased sympathetic tonus and ongoing PVN neuronal activity. The increased sensitivity of Na+/osmosensitive circuitry in CIH-exposed rats suggests that early neuroadaptive responses among body fluid regulatory neurons could contribute to the initiation of CIH hypertension.


2021 ◽  
Vol 15 ◽  
Author(s):  
Xiao-Jing Yu ◽  
Tong Xiao ◽  
Xiao-Jing Liu ◽  
Ying Li ◽  
Jie Qi ◽  
...  

The incidence rate and mortality of hypertension increase every year. Hypothalamic paraventricular nucleus (PVN) plays a critical role on the pathophysiology of hypertension. It has been demonstrated that the imbalance of neurotransmitters including norepinephrine (NE), glutamate (Glu) and γ-aminobutyric acid (GABA) are closely related to sympathetic overactivity and pathogenesis of hypertension. N-methyl-D-aspartate receptor (NMDAR), consisting of GluN1 and GluN2 subunits, is considered to be a glutamate-gated ion channel, which binds to Glu, and activates neuronal activity. Studies have found that the synthesis of respiratory chain enzyme complex was affected and mitochondrial function was impaired in spontaneously hypertensive rats (SHR), further indicating that mitochondria is associated with hypertension. Nuclear respiratory factor 1 (Nrf1) is a transcription factor that modulates mitochondrial respiratory chain and is related to GluN1, GluN2A, and GluN2B promoters. However, the brain mechanisms underlying PVN Nrf1 modulating sympathoexcitation and blood pressure during the development of hypertension remains unclear. In this study, an adeno-associated virus (AAV) vector carrying the shRNA targeting rat Nrf1 gene (shNrf1) was injected into bilateral PVN of male rats underwent two kidneys and one clip to explore the role of Nrf1 in mediating the development of hypertension and sympathoexcitation. Administration of shNrf1 knocked down the expression of Nrf1 and reduced the expression of excitatory neurotransmitters, increased the expression of inhibitory neurotransmitters, and reduced the production of reactive oxygen species (ROS), and attenuated sympathoexcitation and hypertension. The results indicate that knocking down Nrf1 suppresses sympathoexcitation in hypertension by reducing PVN transcription of NMDAR subunits (GluN1, GluN2A, and GluN2B), rebalancing PVN excitatory and inhibitory neurotransmitters, inhibiting PVN neuronal activity and oxidative stress, and attenuating sympathetic activity.


2005 ◽  
Vol 494 (4) ◽  
pp. 673-685 ◽  
Author(s):  
Sean D. Stocker ◽  
Johnny R. Simmons ◽  
Ruth L. Stornetta ◽  
Glenn M. Toney ◽  
Patrice G. Guyenet

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