High oxygen prevents fetal lethality due to lack of catecholamines

Ream, Margie A.; Chandra, Rashmi; Peavey, Mary; Ray, Alisa; Roffler-Tarlov, Suzanne; Kim, Hyunggun; Wetsel, William C.; Rockman, Howard A.; Chikaraishi, Dona M.

doi:10.1152/ajpregu.00860.2007

Cited by 19 publications

(11 citation statements)

References 55 publications

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“…Heart rates in H2CKOs are significantly slower than control littermates. This phenotype is consistent with previous publications on genetic models of catecholamine deficiency, such as Epas1 null mice, which are reported to have low catecholamine levels and a pronounced bradycardia (Tian et al, 1998), as well as Th null embryos, which are reported to have a 28% reduction in heart rate (Ream et al, 2008). In contrast, no difference in PR interval was observed between controls and H2CKOs , and while P-wave duration and QRS complex duration both trended toward an increase, no significant differences were observed, indicating that conditional ablation of Hand2 does not alter dromotropic properties of the P3 heart.…”

Section: Discussionsupporting

confidence: 92%

Loss of Hand2 in a population of Periostin lineage cells results in pronounced bradycardia and neonatal death

VanDusen

Vincentz

Firulli

et al. 2014

Developmental Biology

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The Periostin Cre (Postn-Cre) lineage includes endocardial and neural crest derived mesenchymal cells of the cardiac cushions, neural crest-derived components of the sympathetic and enteric nervous systems, and cardiac fibroblasts. In this study, we use the Postn-Cre transgenic allele to conditionally ablate Hand2 (H2CKO). We find that Postn-Cre H2CKOs die shortly after birth despite a lack of obvious cardiac structural defects. To ascertain the cause of death, we performed a detailed comparison of the Postn-Cre lineage and Hand2 expression at mid and late stages of embryonic development. Gene expression analyses demonstrate that Postn-Cre ablates Hand2 from the adrenal medulla as well as the sphenopalatine ganglia of the head. In both cases, Hand2 loss-of-function dramatically reduces expression of Dopamine Beta Hydroxylase (Dbh), a gene encoding a crucial catecholaminergic biosynthetic enzyme. Expression of the genes Tyrosine Hydroxylase (Th) and Phenylethanolamine N-methyltransferase (Pnmt), which also encode essential catecholaminergic enzymes, were severely reduced in postnatal adrenal glands. Electrocardiograms demonstrate that 3-day postnatal Postn-Cre H2CKO pups exhibit sinus bradycardia. In conjunction with the aforementioned gene expression analyses, these results strongly suggest that the observed postnatal lethality occurs due to a catecholamine deficiency and subsequent heart failure.

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Section: Discussionsupporting

confidence: 92%

Loss of Hand2 in a population of Periostin lineage cells results in pronounced bradycardia and neonatal death

VanDusen

Vincentz

Firulli

et al. 2014

Developmental Biology

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“…These Hif2α−/− embryos die in midgestation similarly to TH- or DBH-deficient mice (Kobayashi et al, 1995; Thomas et al, 1995; Zhou et al, 1995), emphasising the importance of catecholamines during mammalian development. This crucial requirement is reinforced by findings that maternal oxygen (inspired O 2 33 or 63%) prevents mid-gestational lethality of TH-deficient embryos indicating that catecholamines mediate fetal survival by maintaining oxygen homeostasis (Ream, et al, 2008). …”

Section: Regulation Of Catecholamine Synthesis and Secretion By Hmentioning

confidence: 98%

“…Direct effects of hypoxia on chromaffin cell catecholamine release are vital for maintaining physiological homeostasis of foetuses before sympathetic innervation is fully developed (Phillippe, 1983; Ream et al, 2008). Increased release of catecholamines at birth facilitates appropriate haemodynamic adjustments and stimulation of surfactant production by the lungs (Padbury, 1989; Paulick et al, 1985).…”

Section: Regulation Of Catecholamine Synthesis and Secretion By Hmentioning

confidence: 99%

Role of Hypoxia and HIF2α in Development of the Sympathoadrenal Cell Lineage and Chromaffin Cell Tumors with Distinct Catecholamine Phenotypic Features

Richter

Qin

Pacák³

et al. 2013

Advances in Pharmacology

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Hypoxia has wide-ranging impact in normal physiology and disease processes. This stimulus evokes changes in gene expression mediated by transcription factors termed hypoxia-inducible factors (HIFs) that affect numerous processes: angiogenesis, cell survival, cellular metabolism, stem cell self- renewal and multipotency, migration, invasiveness and metastatic progression in tumour cells. Over the past decade increasing numbers of reports have emerged documenting differential roles of HIF1α and HIF2α in these processes. In cells of the sympathoadrenal lineage both HIFs differentially mediate influences of hypoxia on catecholamine synthesis and secretion, but HIF2α signalling has particularly prominent functions in regulating developmental processes of growth and differentiation. This article discusses the role of HIF2α and HIF1α in the context of the development, phenotypic features and functions of chromaffin cells. Moreover, current knowledge about tumour formation in cells of the sympathoadrenal lineage, leading to catecholamine producing pheochromocytomas and paragangliomas, is analysed in the light of the HIF2α signalling network.

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“…The latter involves the stimulation of surfactant secretion via β 2 -receptors, and transformation of the physiological properties of the lung epithelium from a state where fluid is secreted to one where fluid is reabsorbed (Olver et al, 1986;Van Woudenberg et al, 2012). In the developing rat embryo, the release of CAT during hypoxic stress has been proposed to promote fetal survival by reversing hypoxia-induced bradycardia, thereby maintaining O 2 homeostasis (Ream et al, 2008). Also, in fetal sheep, CAT release during hypoxia maintains peripheral vasoconstriction and aids in the redistribution of cardiac output away from non-essential organs (e.g.…”

Section: Introductionmentioning

confidence: 99%

Ontogeny of O2 and CO2//H+ chemosensitivity in adrenal chromaffin cells: role of innervation

Salman

Buttigieg

Nurse

2014

Journal of Experimental Biology

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The adrenal medulla plays a key role in the physiological responses of developing and mature mammals by releasing catecholamines (CAT) during stress. In rodents and humans, the innervation of CATproducing, adrenomedullary chromaffin cells (AMCs) is immature or absent during early postnatal life, when these cells possess 'direct' hypoxia-and CO 2 /H + -chemosensing mechanisms. During asphyxial stressors at birth, these mechanisms contribute to a CAT surge that is critical for adaptation to extra-uterine life. These direct chemosensing mechanisms regress postnatally, in parallel with maturation of splanchnic innervation. Here, we review the evidence that neurotransmitters released from the splanchnic nerve during innervation activate signaling cascades that ultimately cause regression of direct AMC chemosensitivity to hypoxia and hypercapnia. In particular, we consider the roles of cholinergic and opioid receptor signaling, given that splanchnic nerves release acetylcholine and opiate peptides onto their respective postsynaptic nicotinic and opioid receptors on AMCs. Recent in vivo and in vitro studies in the rat suggest that interactions involving α7 nicotinic acetylcholine receptors (nAChRs), the hypoxia inducible factor (HIF)-2α signaling pathway, protein kinases and ATP-sensitive K + (K ATP ) channels contribute to the selective suppression of hypoxic chemosensitivity. In contrast, interactions involving μ-and/or δ-opiod receptor signaling pathways contribute to the suppression of both hypoxic and hypercapnic chemosensitivity, via regulation of the expression of K ATP channels and carbonic anhydrase (CA I and II), respectively. These data suggest that the ontogeny of O 2 and CO 2 /H + chemosensitivity in chromaffin cells can be regulated by the tonic release of presynaptic neurotransmitters.

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High oxygen prevents fetal lethality due to lack of catecholamines

Abstract: Ream MA, Chandra R, Peavey M, Ray AM, Roffler-Tarlov S, Kim H-G, Wetsel WC, Rockman HA, Chikaraishi DM. High oxygen prevents fetal lethality due to lack of catecholamines.

Cited by 19 publications

References 55 publications

Loss of Hand2 in a population of Periostin lineage cells results in pronounced bradycardia and neonatal death

Loss of Hand2 in a population of Periostin lineage cells results in pronounced bradycardia and neonatal death

Role of Hypoxia and HIF2α in Development of the Sympathoadrenal Cell Lineage and Chromaffin Cell Tumors with Distinct Catecholamine Phenotypic Features

Ontogeny of O2 and CO2//H+ chemosensitivity in adrenal chromaffin cells: role of innervation

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