scholarly journals Acute hypoxia activates neuroendocrine, but not presympathetic, neurons in the paraventricular nucleus of the hypothalamus: differential role of nitric oxide

2017 ◽  
Vol 312 (6) ◽  
pp. R982-R995 ◽  
Author(s):  
K. Max Coldren ◽  
De-Pei Li ◽  
David D. Kline ◽  
Eileen M. Hasser ◽  
Cheryl M. Heesch
Keyword(s):  
Nitric Oxide ◽  
Paraventricular Nucleus ◽  
Median Eminence ◽  
Nucleus Tractus Solitarius ◽  
Acute Hypoxia ◽  
Ventrolateral Medulla ◽  
Specific Cell ◽  
External Zone ◽  
Cell Phenotypes

Hypoxia results in decreased arterial Po2, arterial chemoreflex activation, and compensatory increases in breathing, sympathetic outflow, and neuroendocrine secretions, including increased secretion of AVP, corticotropin-releasing hormone (CRH), adrenocorticotropin hormone (ACTH), and corticosterone. In addition to a brain stem pathway, including the nucleus tractus solitarius (nTS) and the rostral ventrolateral medulla (RVLM), medullary pathways to the paraventricular nucleus of the hypothalamus (PVN) contribute to chemoreflex responses. Experiments evaluated activation of specific cell phenotypes within the PVN following an acute hypoxic stimulus (AH; 2 h, 10% O2) in conscious rats. Retrograde tracers (from spinal cord and RVLM) labeled presympathetic (PreS) neurons, and immunohistochemistry identified AVP- and CRH-immunoreactive (IR) cells. c-Fos-IR was an index of neuronal activation. Hypoxia activated AVP-IR (~6%) and CRH-IR (~15%) cells, but not PreS cells in the PVN, suggesting that sympathoexcitation during moderate AH is mediated mainly by a pathway that does not include PreS neurons in the PVN. Approximately 14 to 17% of all PVN cell phenotypes examined expressed neuronal nitric oxide synthase (nNOS-IR). AH activated only nNOS-negative AVP-IR neurons. In contrast ~23% of activated CRH-IR neurons in the PVN contained nNOS. In the median eminence, CRH-IR terminals were closely opposed to tanycyte processes and end-feet (vimentin-IR) in the external zone, where vascular NO participates in tanycyte retraction to facilitate neuropeptide secretion into the pituitary portal circulation. Results are consistent with an inhibitory role of NO on AVP and PreS neurons in the PVN and an excitatory role of NO on CRH secretion in the PVN and median eminence.

Role of Nitric Oxide Synthase Uncoupling at Rostral Ventrolateral Medulla in Redox-Sensitive Hypertension Associated With Metabolic Syndrome

Hypertension ◽  
2014 ◽  
Vol 64 (4) ◽  
pp. 815-824 ◽  
Author(s):  
Kay L.H. Wu ◽  
Yung-Mei Chao ◽  
Shiow-Jen Tsay ◽  
Chen Hsiu Chen ◽  
Samuel H.H. Chan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Metabolic Syndrome ◽  
Nitric Oxide Synthase ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Oxide Synthase

scholarly journals Regulation of Serine (Ser)-31 and Ser40 Tyrosine Hydroxylase Phosphorylation during Morphine Withdrawal in the Hypothalamic Paraventricular Nucleus and Nucleus Tractus Solitarius-A2 Cell Group: Role of ERK1/2

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 5780-5793 ◽  
Author(s):  
Cristina Núñez ◽  
M. Luisa Laorden ◽  
M. Victoria Milanés
Keyword(s):  
Tyrosine Hydroxylase ◽  
Paraventricular Nucleus ◽  
Nucleus Tractus Solitarius ◽  
Morphine Withdrawal ◽  
Hypothalamic Paraventricular Nucleus ◽  
Cell Group ◽  
Erk Activation ◽  
Catecholamine Biosynthesis ◽  
Hpa Axis Activity

Our previous studies have shown that naloxone-induced morphine withdrawal increases the hypothalamic-pituitary-adrenocortical (HPA) axis activity, which is dependent on a hyperactivity of noradrenergic pathways [nucleus tractus solitarius (NTS) A2] innervating the hypothalamic paraventricular nucleus (PVN). Short-term regulation of catecholamine biosynthesis occurs through phosphorylation of tyrosine hydroxylase (TH), which enhances enzymatic activity. In the present study, the effect of morphine withdrawal on site-specific TH phosphorylation in the PVN and NTS-A2 was determined by quantitative blot immunolabeling and immunohistochemistry using phosphorylation state-specific antibodies. We show that naloxone-induced morphine withdrawal phosphorylates TH at Serine (Ser)-31 but not Ser40 in PVN and NTS-A2, which is associated with both an increase in total TH immunoreactivity in NTS-A2 and an enhanced TH activity in the PVN. In addition, we demonstrated that TH neurons phosphorylated at Ser31 coexpress c-Fos in NTS-A2. We then tested whether pharmacological inhibition of ERK activation by ERK kinase contributes to morphine withdrawal-induced phosphorylation of TH at Ser31. We show that the ability of morphine withdrawal to stimulate phosphorylation at this seryl residue is reduced by SL327, an inhibitor of ERK1/2 activation. These results suggest that morphine withdrawal increases noradrenaline turnover in the PVN, at least in part, via ERK1/2-dependent phosphorylation of TH at Ser31.

Exercise training improves endogenous nitric oxide mechanisms within the paraventricular nucleus in rats with heart failure

2005 ◽  
Vol 288 (5) ◽  
pp. H2332-H2341 ◽  
Author(s):  
Hong Zheng ◽  
Yi-Fan Li ◽  
Kurt G. Cornish ◽  
Irving H. Zucker ◽  
Kaushik P. Patel
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Exercise Training ◽  
Paraventricular Nucleus ◽  
No Donor ◽  
Protein Levels ◽  
Arterial Blood ◽  
Endogenous Nitric Oxide ◽  
Dose Dependent

Previously, we have demonstrated that an altered endogenous nitric oxide (NO) mechanism within the paraventricular nucleus (PVN) contributes to increased renal sympathetic nerve activity (RSNA) in heart failure (HF) rats. The goal of this study was to examine the effect of exercise training (ExT) in improving the endogenous NO mechanism within the PVN involved in the regulation of RSNA in rats with HF. ExT significantly restored the decreased number of neuronal NO synthase (nNOS)-positive neurons in the PVN (129 ± 17 vs. 99 ± 6). nNOS mRNA expression and protein levels in the PVN were also significantly increased in HF-ExT rats compared with HF-sedentary rats. To examine the functional role of NO within the PVN, an inhibitor of NOS, NG-monomethyl-l-arginine, was microinjected into the PVN. Dose-dependent increases in RSNA, arterial blood pressure (BP), and heart rate (HR) were produced in all rats. There was a blunted increase in these parameters in HF rats compared with the sham-operated rats. ExT significantly augmented RSNA responses in rats with HF (33% vs. 20% at the highest dose), thus normalizing the responses. The NO donor sodium nitroprusside, microinjected into the PVN, produced dose-dependent decreases in RSNA, BP, and HR in both sham and HF rats. ExT significantly improved the blunted decrease in RSNA in HF rats (36% vs. 17% at the highest dose). In conclusion, our data indicate that ExT improves the altered NO mechanism within the PVN and restores NO-mediated changes in RSNA in rats with HF.

scholarly journals Acute systemic hypoxia activates hypothalamic paraventricular nucleus-projecting catecholaminergic neurons in the caudal ventrolateral medulla

2013 ◽  
Vol 305 (10) ◽  
pp. R1112-R1123 ◽  
Author(s):  
T. Luise King ◽  
David D. Kline ◽  
Brian C. Ruyle ◽  
Cheryl M. Heesch ◽  
Eileen M. Hasser
Keyword(s):  
Paraventricular Nucleus ◽  
Acute Hypoxia ◽  
Hypothalamic Paraventricular Nucleus ◽  
Ventrolateral Medulla ◽  
Caudal Ventrolateral Medulla ◽  
Catecholaminergic Neurons ◽  
Systemic Hypoxia ◽  
Neuroendocrine Responses ◽  
Catecholamine Neurons ◽  
Catecholaminergic Cells

Hypoxia activates catecholamine neurons in the caudal ventrolateral medulla (CVLM). The hypothalamic paraventricular nucleus (PVN) modulates arterial chemoreflex responses and receives catecholaminergic projections from the CVLM, but it is not known whether the CVLM-PVN projection is activated by chemoreflex stimulation. We hypothesized that acute hypoxia (AH) activates PVN-projecting catecholaminergic neurons in the CVLM. Fluoro-Gold (2%, 60–90 nl) was microinjected into the PVN of rats to retrogradely label CVLM neurons. After recovery, conscious rats underwent 3 h of normoxia (21% O2, n = 4) or AH (12, 10, or 8% O2; n = 5 each group). We used Fos immunoreactivity as an index of CVLM neuronal activation and tyrosine hydroxylase (TH) immunoreactivity to identify catecholaminergic neurons. Positively labeled neurons were counted in six caudal-rostral sections containing CVLM. Hypoxia progressively increased the number of Fos-immunoreactive CVLM cells (21%, 19 ± 6; 12%, 49 ± 2; 10%, 117 ± 8; 8%, 179 ± 7; P < 0.001). Catecholaminergic cells colabeled with Fos immunoreactivity in the CVLM were observed following 12% O2, and further increases in hypoxia severity caused markedly more activation. PVN-projecting CVLM cells were activated following more severe hypoxia (10% and 8% O2). A large proportion (89 ± 3%) of all activated PVN-projecting CVLM neurons were catecholaminergic, regardless of hypoxia intensity. Data suggest that catecholaminergic, PVN-projecting CVLM neurons are particularly hypoxia-sensitive, and these neurons may be important in the cardiorespiratory and/or neuroendocrine responses elicited by the chemoreflex.

scholarly journals Hypoxia activates nucleus tractus solitarii neurons projecting to the paraventricular nucleus of the hypothalamus

2012 ◽  
Vol 302 (10) ◽  
pp. R1219-R1232 ◽  
Author(s):  
T. Luise King ◽  
Cheryl M. Heesch ◽  
Catharine G. Clark ◽  
David D. Kline ◽  
Eileen M. Hasser
Keyword(s):  
Arterial Pressure ◽  
Paraventricular Nucleus ◽  
Acute Hypoxia ◽  
Brain Regions ◽  
Nucleus Tractus Solitarii ◽  
Ventrolateral Medulla ◽  
Peripheral Chemoreceptor ◽  
Cardiorespiratory Function ◽  
Afferent Information ◽  
Fos Expression

Peripheral chemoreceptor afferent information is sent to the nucleus tractus solitarii (nTS), integrated, and relayed to other brain regions to alter cardiorespiratory function. The nTS projects to the hypothalamic paraventricular nucleus (PVN), but activation and phenotype of these projections during chemoreflex stimulation is unknown. We hypothesized that activation of PVN-projecting nTS neurons occurs primarily at high intensities of hypoxia. We assessed ventilation and cardiovascular parameters in response to increasing severities of hypoxia. Retrograde tracers were used to label nTS PVN-projecting neurons and, in some rats, rostral ventrolateral medulla (RVLM)-projecting neurons. Immunohistochemistry was performed to identify nTS cells that were activated (Fos-immunoreactive, Fos-IR), catecholaminergic, and GABAergic following hypoxia. Conscious rats underwent 3 h normoxia ( n = 4, 21% O2) or acute hypoxia (12, 10, or 8% O2; n = 5 each). Hypoxia increased ventilation and the number of Fos-IR nTS cells (21%, 13 ± 2; 12%, 58 ± 4; 10%, 166 ± 22; 8%, 186 ± 6). Fos expression after 10% O2was similar whether arterial pressure was allowed to decrease (−13 ± 1 mmHg) or was held constant. The percentage of PVN-projecting cells activated was intensity dependent, but contrary to our hypothesis, PVN-projecting nTS cells exhibiting Fos-IR were found at all hypoxic intensities. Notably, at all intensities of hypoxia, ∼75% of the activated PVN-projecting nTS neurons were catecholaminergic. Compared with RVLM-projecting cells, a greater percentage of PVN-projecting nTS cells was activated by 10% O2. Data suggest that increasing hypoxic intensity activates nTS PVN-projecting cells, especially catecholaminergic, PVN-projecting neurons. The nTS to PVN catecholaminergic pathway may be critical even at lower levels of chemoreflex activation and more important to cardiorespiratory responses than previously considered.

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