Nitric oxide inhibition abolishes sleep-wake differences in cerebral circulation

Zoccoli, Giovanna; Grant, Daniel; Wild, Jennene; Walker, Adrian M.

doi:10.1152/ajpheart.2001.280.6.h2598

Cited by 25 publications

(21 citation statements)

References 50 publications

(78 reference statements)

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“…The cholinergic agents used in this study may have acted indirectly 671 through the release of nitric oxide. Nitric oxide synthase inhibition in the newborn lamb prevents the increase in blood flow normally observed in the sagittal sinus during REM sleep (34).…”

Section: Discussionmentioning

confidence: 98%

“…Carbachol injection in the basal forebrain causes an increase in acetylcholine in the parietal cortex (14), suggesting that although our drug injection was into the cerebrospinal fluid bathing the pons and medulla, we may have influenced brain areas beyond this region. Nitric oxide (34) and oxygen diffusion limitation in the brain (7) also play a role in mediating CBF changes observed during different sleep states. The cholinergic agents used in this study may have acted indirectly 671 through the release of nitric oxide.…”

Section: Discussionmentioning

confidence: 99%

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Cerebral Blood Flow during Spontaneous and Cholinergically Induced Behavioral States in the Sheep Fetus

et al. 2005

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The sleep-wake cycle has been studied extensively in both adult and fetal mammalian species with emphasis in different areas. Fetal studies have focused on characterization of behavioral states and responses to challenges such as hypoxia, and there have been relatively fewer studies that have investigated the control of fetal behavioral state. The objective of this study was to determine whether cerebral blood flow during cholinergically induced fetal behavioral states was similar to that during spontaneous fetal behavioral states in chronically catheterized near-term sheep fetuses. Injection of carbachol (1.25 g) into the cisterna magna increased the duration of the subsequent lowvoltage electrocortical epoch. Scopolamine infusion (0.3 mg) increased the duration of the subsequent high-voltage electrocortical activity epoch. Cerebral blood flow and oxygen delivery were higher during both spontaneous and carbachol-induced low-voltage/rapid eye movement behavioral state than during spontaneous and scopolamine-induced high-voltage/non-rapid eye movement behavioral state. Thus, pharmacologic manipulation of fetal behavioral state induced a state that resembled spontaneous fetal behavioral state both electrophysiologically and metabolically. This study shows that inducing extended periods of a desired fetal behavioral state is possible and that this method may be used to study their function. Cycles of behavioral state are present before birth in species in which significant brain development occurs in utero, including the rhesus monkey, guinea pig, and sheep. After 120 d gestation (term ϭ 145 Ϯ 3 d), the sheep fetus cycles between a low-voltage (LV)/rapid eye movement (REM) behavioral state-characterized by LV fast electrocortical activity, rapid eye movements, and nuchal muscle atonia-and a high-voltage (HV)/non-rapid eye movement (NREM) behavioral statecharacterized by HV slow electrocortical activity, no eye movements, and nuchal muscle tone (1) every 30 -40 min (2). Near term, after 135 d, the sheep fetus exhibits short periods of "wakefulness" as defined by LV fast electrocortical activity and nuchal muscle tone (3,4). In addition, cerebral metabolic rate (CMR) of oxygen and cerebral blood flow (CBF) are increased during LV/REM compared with HV/NREM behavioral state (5). These fetal behavioral states are electrophysiologically similar to the REM and NREM sleep states observed during adult sleep, and higher CBF has been measured during REM sleep compared with NREM sleep in all adult mammals studied (6 -8).Cholinergic drugs also alter REM and NREM sleep in adult species. Microinjection of carbachol into brainstem nuclei of the pontine reticular formation increases REM episodes in rats (9). Likewise, rats that are treated with s.c. infusion of scopolamine exhibit a decrease in sleep, with greater suppression of REM than NREM sleep (10). In the sheep fetus, a 90-min infusion of carbachol increases the incidence of LV/REM behavioral state (11,12), whereas scopolamine administration increases the incidence of HV/NREM...

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Cerebral Blood Flow during Spontaneous and Cholinergically Induced Behavioral States in the Sheep Fetus

et al. 2005

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“…There might be quantitative dierences with waking CBF regulation. For example, in lambs, NO has a major in¯uence on CBF during sleep as well as during wakefulness and its eects seem quantitatively dierent depending on sleep stage (Zoccoli et al 1998). Likewise, local levels of adenosine are lower during sleep than during wakefulness (Porkka-Heiskanen et al 1997) and might modulate local blood¯ow dierently in sleep.…”

Section: Cerebral Blood¯ow As a Marker Of Neuronal Activity During Sleepmentioning

confidence: 99%

Functional neuroimaging of normal human sleep by positron emission tomography

Maquet

2000

Journal of Sleep Research

562

312

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Functional neuroimaging using positron emission tomography has recently yielded original data on the functional neuroanatomy of human sleep. This paper attempts to describe the possibilities and limitations of the technique and clarify its usefulness in sleep research. A short overview of the methods of acquisition and statistical analysis (statistical parametric mapping, SPM) is presented before the results of PET sleep studies are reviewed. The discussion attempts to integrate the functional neuroimaging data into the body of knowledge already acquired on sleep in animals and humans using various other techniques (intracellular recordings, in situ neurophysiology, lesional and pharmacological trials, scalp EEG recordings, behavioural or psychological description). The published PET data describe a very reproducible functional neuroanatomy in sleep. The core characteristics of this ‘canonical’ sleep may be summarized as follows. In slow‐wave sleep, most deactivated areas are located in the dorsal pons and mesencephalon, cerebellum, thalami, basal ganglia, basal forebrain/hypothalamus, prefrontal cortex, anterior cingulate cortex, precuneus and in the mesial aspect of the temporal lobe. During rapid‐eye movement sleep, significant activations were found in the pontine tegmentum, thalamic nuclei, limbic areas (amygdaloid complexes, hippocampal formation, anterior cingulate cortex) and in the posterior cortices (temporo‐occipital areas). In contrast, the dorso‐lateral prefrontal cortex, parietal cortex, as well as the posterior cingulate cortex and precuneus, were the least active brain regions. These preliminary studies open up a whole field in sleep research. More detailed explorations of sleep in humans are now accessible to experimental challenges using PET and other neuroimaging techniques. These new methods will contribute to a better understanding of sleep functions.

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“…8 The mechanisms behind the reported changes in cerebral vascular regulation are unknown. Research in lambs suggests that nitric oxide (NO) is essential in determining the level of CBF during sleep, 9 and in humans, a trend exists for NO levels to be reduced from evening to morning. 10 From this, it is plausible to suggest that NO could play an important a role in determining the changes in cerebral vascular reactivity during sleep and on awakening in humans.…”

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confidence: 99%

Overnight Changes in the Cerebral Vascular Response to Isocapnic Hypoxia and Hypercapnia in Healthy Humans

Meadows

Kotajima

Vazir

et al. 2005

Stroke

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Background and Purpose-The reduction in hypercapnic cerebral vascular reactivity that occurs in the morning after sleep is associated with an increased risk of cerebral ischemia and stroke. It is not known if the cerebral vascular response to hypoxia is similarly reduced in the morning, but such a reduction could be considered a further risk factor for cerebral vascular disease. Methods-To test if the cerebral vascular response to hypoxia is reduced in the morning, the overnight changes in the left middle cerebral artery velocity (MCAV) in response to isocapnic hypoxia (IH) and hypercapnia before and after a normal night sleep were determined in 18 individuals. Results-From evening to morning, hypercapnic cerebral vascular reactivity decreased significantly (evening 2.0Ϯ0.4, morning 1.3Ϯ0.2 cm/sec/mm Hg; PϽ0.05); in contrast, the increase in MCAV in response to IH (Ϫ10% SaO 2 ) was unchanged (evening 9.0Ϯ1.4, morning 8.7Ϯ2.2%; PϾ0.05). Conclusions-Our findings indicate that substantial differences exist in the regulation of the cerebral circulation in response to hypoxia and hypercapnia on waking from sleep. An intact cerebral vascular response to IH, during this time period, could be interpreted as a protective mechanism against cerebral ischemia and stroke; this is of particular relevance to patients with obstructive sleep apnea who arouse from sleep during hypoxia.

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Nitric oxide inhibition abolishes sleep-wake differences in cerebral circulation

Cited by 25 publications

References 50 publications

Cerebral Blood Flow during Spontaneous and Cholinergically Induced Behavioral States in the Sheep Fetus

Cerebral Blood Flow during Spontaneous and Cholinergically Induced Behavioral States in the Sheep Fetus

Functional neuroimaging of normal human sleep by positron emission tomography

Overnight Changes in the Cerebral Vascular Response to Isocapnic Hypoxia and Hypercapnia in Healthy Humans

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