Cross‐influence of membrane polyunsaturated fatty acids and hypoxia‐reoxygenation on α‐ and β‐adrenergic function of rat cardiomyocytes

Ponsard, Blandine; Durot, Isabelle; Delerive, Philippe; Oudot, Fabien; Cordelet, Catherine; Grynberg, Alain; Athias, Pierre

doi:10.1007/s11745-999-0385-5

Cited by 15 publications

(13 citation statements)

References 36 publications

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“…Hypoxia reduces heart rate in adult and perinatal atrial strips [51][52][53] and cardiomyocytes [54][55][56] , suggesting that a bradycardic response to hypoxia is intrinsic to adult and perinatal cardiac cells. However, the effect of hypoxia has not been assessed in the early fetal heart.…”

Section: In Isolated Fetal Hearts Hypoxia Induces Bradycardia Which mentioning

confidence: 99%

β<sub>1</sub>-Adrenergic Receptors Maintain Fetal Heart Rate and Survival

et al. 2006

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β-Adrenergic receptor (βAR) activation has been shown to maintain heart rate during hypoxia and to rescue the fetus from the fetal lethality that occurs in the absence of norepinephrine. This study examines whether the same subtype of βAR is responsible for survival and heart rate regulation. It also investigates which βARs are located on the early fetal heart and whether they can be directly activated during hypoxia. Cultured E12.5 mouse fetuses were treated with subtype-specific βAR antagonists to pharmacologically block βARs during a hypoxic insult. Hypoxia alone reduced heart rate by 35–40% compared to prehypoxic levels. During hypoxia, heart rate was further reduced by 31% in the presence of a β₁AR antagonist, CGP20712A, at 100 nM, but not with a β₂ (ICI118551)- or a β₃ (SR59230A)-specific antagonist at 100 nM. Survival in utero was also mediated by β₁ARs. A β₁ partial agonist, xamoterol, rescued 74% of catecholamine-deficient (tyrosine-hydroxylase-null) pups to birth, a survival rate equivalent to that with a nonspecific βAR agonist, isoproterenol (87%). Receptor autoradiography showed that β₁ARs were only found on the mouse heart at E12.5, while β₂ARs were localized to the liver and vasculature. To determine if the response to hypoxia was intrinsic to the heart, isolated fetal hearts were incubated under hypoxic conditions in the presence of a βAR agonist. Heart rate was reduced to 25–30% by hypoxia alone, but was restored to 63% of prehypoxic levels with 100 nM isoproterenol. Restoration was completely prevented if β₁ARs were blocked with CGP20712A at 300 nM, a concentration that blocks β₁ARs, but not β₂- or β₃ARs. Our results demonstrate that β₁ARs are located on the heart of early fetal mice and that β₁AR stimulation maintains fetal heart rate during hypoxia and mediates survival in vivo.

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Section: In Isolated Fetal Hearts Hypoxia Induces Bradycardia Which mentioning

confidence: 99%

β<sub>1</sub>-Adrenergic Receptors Maintain Fetal Heart Rate and Survival

et al. 2006

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“…Another adipokine, tumor necrosis factor-α (TNFα) is released as a consequence of inflammatory responses and acts as an autocrine/paracrine signal to regulate the function of other adipokines, insulin and other critical metabolic factors [16]; TNFα contributes to insulin resistance and diabetes, and the adipose inflammatory response is thought to play a significant role in obesity [3,45]. In turn, systemic changes in lipid metabolism and adiposity affect the composition of synaptic membranes within the brain, altering the function of the neurotransmitter receptors and signaling molecules that are embedded in the lipid milieu [6,12,14,19,31]. This may explain why the synaptic and behavioral effects of early-life organophosphate exposure do not represent simply the continuing effects of initial damage, but rather evolve over an extended period from juvenile stages through adolescence and adulthood [37,41,43], concurrently with the emergence of metabolic dysfunction and changes in weight and adiposity [20,21,33].…”

Section: Introductionmentioning

confidence: 99%

Neonatal exposure to parathion alters lipid metabolism in adulthood: Interactions with dietary fat intake and implications for neurodevelopmental deficits

Lassiter

Ryde

Levin

et al. 2010

Brain Research Bulletin

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Organophosphates are developmental neurotoxicants but recent evidence also points to metabolic dysfunction. We determined whether neonatal parathion exposure in rats has long-term effects on regulation of adipokines and lipid peroxidation. We also assessed the interaction of these effects with increased fat intake. Rats were given parathion on postnatal days 1-4 using doses (0.1 or 0.2 mg/kg/ day) that straddle the threshold for barely detectable cholinesterase inhibition and the first signs of systemic toxicity. In adulthood, animals were either maintained on standard chow or switched to a high-fat diet for seven weeks. We assessed serum leptin and adiponectin, tumor necrosis factor-α (TNFα) in adipose tissues, and thiobarbituric acid reactive species (TBARS) in peripheral tissues and brain regions. Neonatal parathion exposure uncoupled serum leptin levels from their dependence on body weight, suppressed adiponectin and elevated TNFα in white adipose tissue. Some of the effects were offset by a high-fat diet. Parathion reduced TBARS in the adipose tissues, skeletal muscle and temporal/occipital cortex but not in heart, liver, kidney or frontal/parietal cortex; it elevated TBARS in the cerebellum; the high-fat diet again reversed many of the effects. Neonatal parathion exposure disrupts the regulation of adipokines that communicate metabolic status between adipose Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. tissues and the brain, while also evoking an inflammatory adipose response. Our results are consistent with impaired fat utilization and prediabetes, as well as exposing a potential relationship between effects on fat metabolism and on synaptic function in the brain. Conflict of Interest NIH Public Access

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“…Alterations in the lipid composition of neural membranes affects neuronal activity, receptor and signaling function, and synaptic transmission [11,20,22,25,32], effects that are likely to contribute to the success of a ketogenic diet in treating intractable epilepsies [8,13,23,24], to pilot studies showing beneficial effects in attentional disorders and autism [13,16,33], and to results in animal models of behavioral deficits [50]. In our earlier work, we found that consumption of a high fat diet in adulthood was able to offset most of the cholinergic synaptic deficits caused by neonatal parathion exposure [37], while at the same time incurring metabolic liabilities [26].…”

Section: Discussionmentioning

confidence: 99%

“…The effects of a high-fat diet on synaptic responses are likely due to global changes in the composition of synaptic membrane lipids [22,32], and therefore can span multiple brain regions and neurotransmitter systems [11,20,25]. In the present work, we explored the lasting effects of neonatal parathion exposure on serotonin (5-hydroxytryptamine, 5HT) pathways in rat brain regions and the effects of dietary manipulation in adulthood on the outcome.…”

Section: Introductionmentioning

confidence: 99%

Neonatal parathion exposure disrupts serotonin and dopamine synaptic function in rat brain regions: Modulation by a high-fat diet in adulthood

Slotkin

Wrench

Ryde

et al. 2009

Neurotoxicology and Teratology

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The consequences of exposure to developmental neurotoxicants are influenced by environmental factors. In the present study, we examined the role of dietary fat intake. We administered parathion to neonatal rats and then evaluated whether a high-fat diet begun in adulthood could modulate the persistent effects on 5HT and DA systems. Neonatal rats received parathion on postnatal days 1-4 at 0.1 or 0.2 mg/kg/day, straddling the cholinesterase inhibition threshold. In adulthood, half the animals in each exposure group were given a high-fat diet for 8 weeks. We assessed 5HT and DA concentrations and turnover in brain regions containing their respective cell bodies and projections. In addition, we monitored 5HT 1A and 5HT 2 receptor binding and the concentration of 5HT presynaptic transporters. Neonatal parathion exposure evoked widespread increases in neurotransmitter turnover, indicative of presynaptic hyperactivity, further augmented by 5HT receptor upregulation. In control rats, consumption of a high-fat diet recapitulated many of the changes seen with neonatal parathion exposure; the effects represented convergent mechanisms, since the high-fat diet often obtunded further increases caused by parathion. Neonatal parathion exposure causes lasting hyperactivity of 5HT and DA systems accompanied by 5HT receptor upregulation, consistent with "miswiring" of neuronal projections. A high-fat diet obtunds the effect of parathion, in part by eliciting similar changes itself. Thus, dietary factors may produce similar synaptic changes as do developmental neurotoxicants, potentially contributing to the increasing incidence in neurodevelopmental disorders.

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Cross‐influence of membrane polyunsaturated fatty acids and hypoxia‐reoxygenation on α‐ and β‐adrenergic function of rat cardiomyocytes

Cited by 15 publications

References 36 publications

β<sub>1</sub>-Adrenergic Receptors Maintain Fetal Heart Rate and Survival

β<sub>1</sub>-Adrenergic Receptors Maintain Fetal Heart Rate and Survival

Neonatal exposure to parathion alters lipid metabolism in adulthood: Interactions with dietary fat intake and implications for neurodevelopmental deficits

Neonatal parathion exposure disrupts serotonin and dopamine synaptic function in rat brain regions: Modulation by a high-fat diet in adulthood

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