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

Abstract

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 beta1-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 Gialpha2 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 beta1-adrenoceptor and an increase in inhibitory G-protein subunit may be caused by increased synaptic NE levels due to impaired uptake-1 system.

• Authors: K Mardon, P Merlet, A Syrota, B Mazière
• Journal: Journal of applied physiology (Bethesda, Md. : 1985) (J Appl Physiol (1985)) Vol. 85 Issue 3 Pg. 890-7 (Sep 1998) ISSN: 8750-7587 [Print] United States
• PMID: 9729562 (Publication Type: Journal Article)

Chemical References

• Receptors, Adrenergic, beta
• GTP-Binding Proteins
• Adenylyl Cyclases
• Norepinephrine
• Epinephrine

Topics

• Adenylyl Cyclases (metabolism)
• Animals
• Atmosphere Exposure Chambers
• Binding, Competitive (physiology)
• Body Weight (physiology)
• Epinephrine (blood)
• GTP-Binding Proteins (metabolism)
• Heart (innervation, physiopathology)
• Hypoxia (metabolism, physiopathology)
• Male
• Myocardium (metabolism)
• Norepinephrine (blood, metabolism)
• Organ Size (physiology)
• Rats
• Rats, Wistar
• Receptors, Adrenergic, beta (metabolism)
• Sympathetic Nervous System (metabolism, physiopathology)
• Synaptic Transmission (physiology)