Antioxidant responses to chronic hypoxia in the rat cerebellum and pons

Ramanathan, Lalini; Gozal, David; Siegel, Jerome M.

doi:10.1111/j.1471-4159.2004.02988.x

Cited by 85 publications

(67 citation statements)

References 38 publications

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“…To determine whether ROS do play a role in chromaffin cell responses to IH, malondialdehyde (MDA) levels in adrenal medullae were monitored as an index of ROS generation Ramanathan et al 2005). The MDA levels were elevated by 60% in adrenal medullae from IH compared with control pups (P Ͻ 0.001; Fig.…”

Section: Ros Signaling Mediates Chromaffin Cell Responses To Ihmentioning

confidence: 99%

Neonatal Intermittent Hypoxia Leads to Long-Lasting Facilitation of Acute Hypoxia-Evoked Catecholamine Secretion From Rat Chromaffin Cells

Souvannakitti

Kumar²,

Fox³

et al. 2009

Journal of Neurophysiology

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Souvannakitti D, Kumar GK, Fox A, Prabhakar NR. Neonatal intermittent hypoxia leads to long-lasting facilitation of acute hypoxia-evoked catecholamine secretion from rat chromaffin cells. J Neurophysiol 101: 2837-2846, 2009. First published April 1, 2009 doi:10.1152/jn.00036.2009. The objective of the present study was to examine the effects of intermittent hypoxia (IH) and sustained hypoxia (SH) on hypoxia-evoked catecholamine (CA) secretion from chromaffin cells in neonatal rats and assess the underlying mechanism(s). Experiments were performed on rat pups exposed to either IH (15-s hypoxia/5-min normoxia; 8 h/day) or SH (hypobaric hypoxia, 0.4 atm) or normoxia (controls) from P0 to P5. IH treatment facilitated hypoxia-evoked CA secretion and elevations in the intracellular calcium ion concentration ([Ca 2ϩ ] i ) and these responses were attenuated, but not abolished, by treatments designed to eliminate Ca 2ϩ flux into cells (Ca 2ϩ -free medium or Cd 2ϩ ), indicating that intracellular Ca 2ϩ stores were augmented by IH. Norepinephrine (NE) and epinephrine (E) levels of adrenal medullae were elevated in IH-treated pups. IH treatment increased reactive oxygen species (ROS) production in adrenal medullae and antioxidant treatment prevented IH-induced facilitation of CA secretion, elevations in [Ca 2ϩ ] i by hypoxia, and the up-regulation of NE and E. The effects of neonatal IH treatment on hypoxia-induced CA secretion and elevation in [Ca 2ϩ ] i , CA, and ROS levels persisted in rats reared under normoxia for Ͼ30 days. In striking contrast, chromaffin cells from SH-treated animals exhibited attenuated hypoxia-evoked CA secretion. In SH-treated cells hypoxiaevoked elevations in [Ca 2ϩ ] i , NE and E contents, and ROS levels were comparable with controls. These observations demonstrate that: 1) neonatal IH and SH evoke opposite effects on hypoxia-evoked CA secretion from chromaffin cells, 2) ROS signaling mediates the faciltatory effects of IH, and 3) the effects of neonatal IH on chromaffin cells persist into adult life. I N T R O D U C T I O NCatecholamine (CA) secretion from the adrenal medulla is critical for maintaining homeostasis under a variety of stress conditions including hypoxia (Lagercrantz and Bistoletti 1977;Seidler and Slotkin 1985). In adult animals, hypoxia-evoked CA secretion from chromaffin cells is neurogenic and requires activation of the sympathetic nervous system (Seidler and Slotkin 1986;Yokotani et al. 2002). In neonates the sympathetic nervous system is not well developed (Seidler and Slotkin 1985). In this case, hypoxia still evokes CA secretion from neonatal chromaffin cells by directly affecting their excitability and elevating intracellular calcium ion concentration ( [Ca 2ϩ ] i ; Takeuchi et al. 2001;Thompson et al. 1997). These studies demonstrate that neonatal chromaffin cells have the ability to sense acute hypoxia similar to the glomus cells of the carotid bodies of adult mammals.Chronic perturbations in environmental O 2 profoundly influence carotid body sensory respo...

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Section: Ros Signaling Mediates Chromaffin Cell Responses To Ihmentioning

confidence: 99%

Neonatal Intermittent Hypoxia Leads to Long-Lasting Facilitation of Acute Hypoxia-Evoked Catecholamine Secretion From Rat Chromaffin Cells

Souvannakitti

Kumar²,

Fox³

et al. 2009

Journal of Neurophysiology

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“…11,12,40 We and others have also shown that IH induces oxidative stress, which induces apoptotic cell losses within the central nervous system in adult and newborn animals, including CV control nuclei. 3,5,6,[41][42][43] Interestingly, when adult rats are exposed to an IH protocol, LV dysfunction occurs and appears to be mediated, at least in part, by increased oxidative stress. 2 Perinatal IH exposures are also associated with plasticity and metaplasticity of neural responses, more specifically as they are related to chemoreceptor, sympathetic, and somatic nerves, all of which may reflect the principal mechanisms underlying the long-term changes in CV control.…”

Section: Blood Pressurementioning

confidence: 99%

Postnatal Intermittent Hypoxia and Developmental Programming of Hypertension in Spontaneously Hypertensive Rats

Soukhova-O'Hare

Ortines

et al. 2008

Hypertension

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Abstract-Obstructive and central apneas during sleep are associated with chronic intermittent hypoxia (CIH) and increased cardiovascular morbidity. Spontaneously hypertensive rats exposed to CIH during postnatal days 4 to 30 develop exaggerated hypertension as adults. We hypothesized that reactive oxygen species and altered L-Ca 2ϩ channel activity may underlie the postnatal programming of exaggerated blood pressure and cardiac remodeling. Newborn male spontaneously hypertensive rats were exposed to CIH (10% and 21% O 2 alternating every 90 seconds, 12 h/d, for postnatal days 4 to 30) or normoxia (room air). In each condition, spontaneously hypertensive rats received daily (SC) 1 of 3 treatments: L-calcium channel blocker nifedipine (5 mg/kg), superoxide dismutase mimetic MnTMPyP pentachloride (10 mg/kg), or vehicle (polyethylene glycol). Blood pressure was evaluated monthly for 6 months after birth, and echocardiographic assessments were conducted at 6 months of age. CIH vehicle-treated rats presented higher systolic blood pressure (187Ϯ5 mm Hg) as compared with normoxic vehicle treated controls (163Ϯ2 mm Hg; PϽ0.001). Postnatal CIH elicited marked increases in left ventricular wall thickness in a pattern of concentric hypertrophy with augmented systolic contractility. The treatment with nifedipine in the CIH group attenuated blood pressure (159Ϯ2 mm Hg; PϽ0.001) and normalized left ventricular wall thickness and systolic function, whereas the treatment with SOD mimetic decreased blood pressure (165Ϯ2 mm Hg; PϽ0.001) and reduced left ventricular wall thickness without changes in the systolic function. We conclude that Ca 2ϩ and reactive oxygen species-mediated signaling during intermittent hypoxia are critical mechanisms underlying postnatal programming of an increased severity of hypertension and hypertrophic cardiac remodeling in a genetically susceptible rodent model. Key Words: intermittent hypoxia Ⅲ calcium channels Ⅲ oxidative stress Ⅲ sleep apnea Ⅲ hypertension I ntermittent hypoxia (IH) during sleep is one of the characteristics of sleep apnea that is associated with substantial cardiovascular (CV) morbidity, such as hypertension and heart failure. Sleep-disordered breathing with apneic episodes and intermittent hypoxemia are frequently encountered in young children 1 ; however, the potential consequences of postnatal IH on adult CV dysfunction are not clear. There is accumulating evidence that IH is associated with an increased oxidative stress [2][3][4][5][6] and that redox signaling during this condition has been extensively implicated in CV pathophysiology, including some forms of hypertension and cardiac function. 2,7-9 Perinatal L-arginine and antioxidant supplements were shown to reduce blood pressure (BP) in adult spontaneously hypertensive rats (SHRs), suggesting a critical role of oxidative status during perinatal development in programming BP later in life. 10 In previous work from our laboratory, we demonstrated that SHRs exposed for the first 30 days of postnatal life to a chronic intermitt...

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“…MDA levels were monitored as an index of lipid peroxidation Ramanathan et al 2005) in untreated (control), H 2 O 2 -treated (2.2 mM for 600 s), and Fe 2ϩ (100 M)-H 2 O 2 (2.2 mM)-treated preBötC and cortico-hippocampal slices. Basal MDA levels were comparable between cortico-hippocampal brain slices and medullary brain slices ( Fig.…”

Section: Effects Of H 2 O 2 On Inspiration-related Neuronal Activity mentioning

confidence: 99%

Hydrogen peroxide differentially affects activity in the pre-Bötzinger complex and hippocampus

Garcia¹,

Khan

Kumar

et al. 2011

Journal of Neurophysiology

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Antioxidant responses to chronic hypoxia in the rat cerebellum and pons

Cited by 85 publications

References 38 publications

Neonatal Intermittent Hypoxia Leads to Long-Lasting Facilitation of Acute Hypoxia-Evoked Catecholamine Secretion From Rat Chromaffin Cells

Neonatal Intermittent Hypoxia Leads to Long-Lasting Facilitation of Acute Hypoxia-Evoked Catecholamine Secretion From Rat Chromaffin Cells

Postnatal Intermittent Hypoxia and Developmental Programming of Hypertension in Spontaneously Hypertensive Rats

Hydrogen peroxide differentially affects activity in the pre-Bötzinger complex and hippocampus

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