Effects of 5-day hypoxia on cardiac adrenergic neurotransmission in rats

Mardon, Karine, Merlet, Pascal, Syrota, André and Mazière, Bernard (1998) Effects of 5-day hypoxia on cardiac adrenergic neurotransmission in rats. Journal of Applied Physiology, 85 3: 890-897.

Author Mardon, Karine
Merlet, Pascal
Syrota, André
Mazière, Bernard
Title Effects of 5-day hypoxia on cardiac adrenergic neurotransmission in rats
Journal name Journal of Applied Physiology   Check publisher's open access policy
ISSN 8750-7587
Publication date 1998-09
Sub-type Article (original research)
Volume 85
Issue 3
Start page 890
End page 897
Total pages 8
Place of publication Bethesda, MD, U.S.A.
Publisher American Physiological Society
Language eng
Formatted abstract
Chronic hypoxia induces an overall sympathetic hyperactivation associated with a myocardial β-receptor desensitization. The mechanisms involved in this desensitization were evaluated in 32 male Wistar rats kept in a hypobaric pressure chamber ( PO2 = 40 Torr, atmospheric pressure = 450 Torr) for 5 days. In hypoxic compared with normoxic conditions, plasma norepinephrine (NE) levels were higher (2.1 ± 0.7 vs. 0.6 ± 0.2 ng/ml) with no difference in the plasma epinephrine levels (2.2 ± 0.7 vs. 1.8 ± 0.3 ng/ml). In hypoxia neuronal NE uptake measured by [3H]NE was decreased by 32% in the right ventricle (RV) and by 35% in the left ventricle (LV), and [3H]mazindol in vitro binding showed a decrease in uptake-1 carrier protein density by 38% in the RV and by 41% in the LV. In vitro binding assays with [3H]CGP-12177 indicate β-adrenoceptor density reduced by 40% in the RV and by 32% in the LV, and this was due to reduced β1-subtype fraction (competition binding experiments with practolol). Hypoxia reduced the production of cAMP induced by isoproterenol (36% decrease in the RV and 41% decrease in the LV), 5′-guanylylimododiphosphate (40% decrease in the RV and 42% decrease in the LV), and forskolin (39% decrease in the RV and 41% decrease in the LV) but did not alter the effect of MnCl2 and NaF. Quantitation of inhibitory G-protein α-subunit by immunochemical analysis showed a 46% increase in the cardiac-specific isoform Formula in hypoxic hearts. The present data demonstrate that in rats 5-day hypoxia leads to changes in pre- and postsynaptic myocardial adrenergic function. The myocardial desensitization associated with both a reduction in externalized β1-adrenoceptor and an increase in inhibitory G-protein subunit may be caused by increased synaptic NE levels due to impaired uptake-1 system.
Copyright © 2011 the American Physiological Society
Keyword Adrenergic neurotransmitters
Uptake 1
Adenylate cyclase
Q-Index Code C1
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Centre for Advanced Imaging Publications
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Created: Thu, 25 Nov 2010, 16:19:43 EST by Dr Karine Mardon on behalf of Centre for Advanced Imaging