Journal of Applied Physiology
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J Appl Physiol 85: 890-897, 1998;
8750-7587/98 $5.00
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Vol. 85, Issue 3, 890-897, September 1998

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

Karine Mardon, Pascal Merlet, André Syrota, and Bernard Mazière

Service Hospitalier Frédéric Joliot, Département de Recherche Médicale, Direction des Sciences du Vivant-Commissariat a l'Énergie Atomique, 91406 Orsay, France

Chronic hypoxia induces an overall sympathetic hyperactivation associated with a myocardial beta -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 beta -adrenoceptor density reduced by 40% in the RV and by 32% in the LV, and this was due to reduced beta 1-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 alpha -subunit by immunochemical analysis showed a 46% increase in the cardiac-specific isoform Gialpha 2 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 beta 1-adrenoceptor and an increase in inhibitory G-protein subunit may be caused by increased synaptic NE levels due to impaired uptake-1 system.

adrenergic neurotransmitters; uptake 1; adenylate cyclase


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