Nitric oxide as a retrograde messenger in the nucleus tractus solitarii of rats during hypoxia.

Ogawa, Hiroyasu; Mizusawa, Akihito; Kikuchi, Yoshihiro; Hida, Wataru; Miki, Hirokazu; Shirato, Kunio

doi:10.1113/jphysiol.1995.sp020828

Cited by 118 publications

(94 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…13,14,24 Indeed, glutamate levels are elevated in the NTS and the medulla during brief hypoxic challenges. 14,15,27 Therefore, the altered pattern of ventilatory response to hypoxia in obese Z rats is suggestive of an altered NMDA receptor mediated mechanism. Lean rats treated with DM have depressed V Ç E relative to saline not only during the early hypoxic response but also during the late hypoxic response, which suggests that endogenously released glutamate modulate both the early and late phase of hypoxic responses in part through NMDA receptors.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

NMDA receptor-mediated modulation of ventilation in obese Zucker rats

2001

View full text Add to dashboard Cite

BACKGROUND: Ventilation in response to hypoxia is reduced in some obese humans and is believed to represent part of the pathogenesis of obesity hypoventilation syndrome (OHS). Ventilation in response to hypoxic exposure is closely related to the release of excitatory neurotransmitters, in particular glutamate, acting speci®cally on N-methyl-D-aspartate (NMDA) receptors. OBJECTIVES: The aim of the present study was to investigate whether NMDA receptor-mediated mechanisms are responsible for the altered ventilatory response to sustained hypoxia observed in obese Zucker (Z) rats. SUBJECTS: Seven lean and seven 15-week-old obese male Z rats were studied. MEASUREMENTS: Ventilation (V Ç E ) at rest and during 30 min sustained hypoxic (10% O 2 ) exposure was measured by the barometric method. V Ç E was assessed following the blinded-random administration of equal volumes of either saline (vehicle) or dextromethorphan (DM, 10 mgakg), a non-competitive glutamate NMDA receptor antagonist. RESULTS: DM had no effects on resting V Ç E in both lean and obese rats during room air breathing. Lean rats treated with DM exhibited a signi®cant (P`0.05) depression in V Ç E , V T , and V T aT I during either the early (5 min) or the late phase (30 min) of ventilatory response to sustained hypoxia. In contrast, DM administration in obese rats did not change V Ç E , V T , or V T aT I during the early phase of ventilatory response to hypoxia. During the late phase of ventilatory response to hypoxia. obese rats treated with DM exhibited a similar depression in V Ç E and V T as observed in lean rats, but had no signi®cant change in V T aT I during the 30 min hypoxic exposure. CONCLUSION: Our ®ndings indicate that altered glutamatergic mechanisms acting on NMDA receptors are partially responsible for a blunted early phase of ventilatory response to hypoxia noted in obese rats and also contribute to their reduced neural respiratory drive.

show abstract

Section: Discussionmentioning

confidence: 99%

“…12,13,24,27 For the current study, however, we selected dextromethorphan (DM) over MK-801 because preliminary studies in our lab demonstrated that low doses of MK-801 (0.1 ± 0.5 mgakg, i.p.) produced restlessness and hyperlocomotion in Z rats, while higher doses of MK-801 (1 ± 5 mgakg, i.p.)…”

Section: Discussionmentioning

confidence: 99%

NMDA receptor-mediated modulation of ventilation in obese Zucker rats

2001

View full text Add to dashboard Cite

show abstract

“…The nitric oxide (NO) in the nucleus tractus solitarii plays an important role on the acute phase during hypoxic stress, and this works as a retrograde messenger in an excitatory transmitter, L-glutamate, releasing a positive feedback system that contributes to the augmentation of ventilation during hypoxia (Mizusawa et al 1994;Ogawa et al 1995). The facilitation of the L-glutamate release system by NO might contribute to the prevention of abrupt changes in ventilation.…”

Section: Discussionmentioning

confidence: 99%

“…1) (Bartlett and Tenney 1970), which was basically the same method as described in previous papers (Mizusawa et al 1994;Ogawa et al 1995) except for the chamber volume used. An unanesthetized and unrestrained mouse was placed in a 700 ml Plexiglass animal chamber connected to a reference chamber of the same volume through a pressure transducer (model MP-45; Validyne, Northridge, CA, USA).…”

Section: Measurement Of Ventilationmentioning

confidence: 99%

“…The targeted fraction concentration of O 2 or CO 2 was obtained within 20 sec, and maintained for 3 min. The ventilatory responses to hypoxia were measured for 15 ~ 20 sec at the peak response during 3 min and those to hypercapnia were measured for the last 15 ~ 20 sec during 3 min (Mizusawa et al 1994;Ogawa et al 1995;Tabata et al 2001;Adachi et al 2004), with an interval of at least 30 min and in random order.…”

Section: Acute Hypoxic and Hypercapnic Ventilatory Responsesmentioning

confidence: 99%

See 1 more Smart Citation

Mice with Blunted Hypoxic Ventilatory Response are Susceptible to Respiratory Disturbance during Hypoxia

Adachi

Ogawa

Okabe

et al. 2006

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Hypoxia causes a life-threatening situation, and the ventilatory response to hypoxia plays an important role in preventing death. We have hypothesized that persons with a blunted hypoxic ventilatory response may have a weak defense response to hypoxic episodes and be susceptible to fatal respiratory disturbances. However, precise correlations between the hypoxic ventilatory response and respiratory disturbances are not well understood. In the present study we examined the hypoxic and hypercapnic ventilatory responses in nine inbred mouse strains (A/J, AKR/N, BALB/c, C3H/He, C57BL/6, DBA/2, NZW, SWR/J, and 129Sv). Breathing frequency, tidal volume and minute ventilation of unanesthetized and unrestrained mice were assessed by whole body plethysmography. Age-matched mice were exposed for 3 min to 10% O 2 in N 2 gas or 10% CO 2 in hyperoxic gas to determine the acute ventilatory response to chemical stimuli. Basal respiratory variables and hypoxic ventilatory responses differed among the strains, but the hypercapnic ventilatory response did not differ. The hypoxic ventilatory response was the highest in AKR/N mice and the lowest in SWR/J mice. These findings suggest that genetic factors may have influenced the hypoxic ventilatory response but not the hypercapnic ventilatory response. To examine the effects of severe hypoxic stress on the respiratory cycle, we exposed the strain with the highest or lowest hypoxic ventilatory response to 6% O 2 in N 2 until the onset of apnea. The "appearance time of apnea", which is defined as the time from the hypoxic loading to the onset of apnea, was shorter in the SWR/J strain than in the AKR/N strain. We suggest that a lower hypoxic ventilatory response may be a risk factor for apnea under hypoxia.

show abstract

Genetic analysis of nitric oxide synthase 1 variants in schizophrenia and bipolar disorder

Silberberg

Ben‐Shachar

Navon

2010

American J of Med Genetics Pt B

View full text Add to dashboard Cite

Nitric oxide (NO) is a neurotransmitter that acts as a second messenger of the N-methyl-D-aspartate receptor and interacts with the dopaminergic and the serotonergic systems. NO involvement in pathological processes relevant to neuropsychiatric disorders stems from its ability to modulate certain forms of synaptic plasticity, and from its capacity to be transformed to a highly active free radical. Additionally, multiple links have been reported between the NO-producing enzyme, nitric oxide synthase (NOS) 1, and both schizophrenia and bipolar disorder (BPD). RNA and DNA isolated from dorsolateral-prefrontal cortices of schizophrenia patients, bipolar patients and controls (n = 26, 30 and 29, respectively) were donated by the Stanley Foundation Brain Collection. Gene expression was measured by Real-Time-PCR. Genetic polymorphisms were genotyped by restriction-fragment length-polymorphism analysis, and by product-size determination of PCR products amplified with a fluorescent primer.Expression analysis of pan-NOS1, as well as of 2 of its isoforms, "NOS1_1d" and "NOS1_1f", which differ in their first exons and translational strength, revealed a trend for pan-NOS1 over-expression (P = 0.075) in schizophrenia patients (1.33-fold), and significant over-expression (P < 0.05) of NOS1_1d and NOS1_1f in this group (1.54-fold and 1.61-fold, respectively). No expressional alteration was observed in BPD. Polymorphisms at the promoters of NOS1_1d and NOS1_1f, previously shown to be functional in vitro, revealed no significant allelic or genotypic differences among clinical groups and showed no effect on these transcripts' expression. In conclusion, understanding the molecular mechanisms underlying the over-expression of specific NOS1 isoforms, which is unique to schizophrenia, may assist in identifying targets for new drugs.

show abstract

Nitric oxide as a retrograde messenger in the nucleus tractus solitarii of rats during hypoxia.

Cited by 118 publications

References 36 publications

NMDA receptor-mediated modulation of ventilation in obese Zucker rats

NMDA receptor-mediated modulation of ventilation in obese Zucker rats

Mice with Blunted Hypoxic Ventilatory Response are Susceptible to Respiratory Disturbance during Hypoxia

Genetic analysis of nitric oxide synthase 1 variants in schizophrenia and bipolar disorder

Contact Info

Product

Resources

About