| High altitude-induced changes in alpha1-adrenergic receptors and Ins(1,4,5)P3 responses in cerebral arteries. | |
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MedLine Citation:
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PMID: 9124493 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In response to high-altitude long-term hypoxemia, the cerebral arteries of fetal and adult sheep show decreased contractile responses to norepinephrine (NE) and other agonists. To test the hypothesis that hypoxia-induced developmental and vessel specific cerebral artery contractility changes are mediated, in part, by changes in alpha1-adrenergic receptor (alpha1-AR) density and/or NE-induced inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] responses, we performed the following study. In common carotid (Com) and main branch cerebral (MBC) arteries from normoxic adult ewes and near-term fetuses and those acclimatized to high altitude (3,820 m), we quantified alpha1-AR density (maximal binding in fmol/mg protein) and affinity (dissociation constant in nM) with the alpha1-AR antagonist [3H]prazosin. In addition, we quantified NE-induced Ins(1,4,5)P3 responses in these arteries. With long-term hypoxemia, alpha1-AR density in fetal and adult Com decreased 75% (from 113 +/- 18 to 28 +/- 5 fmol/mg protein) and 66% (from 54 +/- 3 to 18 +/- 4 fmol/mg protein), respectively, from normoxic control values. alpha1-AR density of the fetal and adult MBC decreased 76% (from 47 +/- 4 to 11 +/- 1 fmol/mg protein) and 61% (from 23 +/- 3 to 9 +/- 3 fmol/mg protein), respectively, from controls. In hypoxemic adult Com, the NE-induced Ins(1,4,5)P3 response decreased 51% (from 309 +/- 38 to 151 +/- 24%) from the control value. In fetal and adult MBC, long-term hypoxemia was associated with decreases of 35% (from 345 +/- 40 to 225 +/- 30%) and 44% (from 355 +/- 55 to 199 +/- 16%), respectively, from control values. We conclude that in the adult Com and MBC vessels, acclimatization to high-altitude, long-term hypoxemia was associated with significant decreases in both alpha1-AR density values and Ins(1,4,5)P3 responses to NE. Similarly, in the fetal MBC arteries, high-altitude hypoxemia was associated with marked attenuation of both alpha1-AR density and NE-induced Ins(1,4,5)P3 responses. The magnitude of decreases in NE-induced Ins(1,4,5)P3 responses in these vessels correlated fairly well with the decreases in alpha1-AR density. These findings suggest that changes in noradrenergic receptor-second messenger coupling may play a role in altered cerebrovascular tone in association with high-altitude acclimatization and other forms of long-term hypoxia in both fetus and adult. |
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Authors:
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N Ueno; Y Zhao; L Zhang; L D Longo |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The American journal of physiology Volume: 272 ISSN: 0002-9513 ISO Abbreviation: Am. J. Physiol. Publication Date: 1997 Feb |
Date Detail:
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Created Date: 1997-04-22 Completed Date: 1997-04-22 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0370511 Medline TA: Am J Physiol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: R669-74 Citation Subset: IM |
Affiliation:
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Department of Physiology, Loma Linda University School of Medicine, California 92350, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acclimatization Adrenergic alpha-Antagonists / metabolism Aging / metabolism Altitude* Animals Anoxia / metabolism Cerebral Arteries / drug effects*, embryology, metabolism* Female Fetus / metabolism Inositol 1,4,5-Trisphosphate / pharmacology* Norepinephrine / pharmacology Prazosin / metabolism Pregnancy Receptors, Adrenergic, alpha / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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HD-03807/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic alpha-Antagonists; 0/Receptors, Adrenergic, alpha; 19216-56-9/Prazosin; 51-41-2/Norepinephrine; 85166-31-0/Inositol 1,4,5-Trisphosphate |
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