Physical activity, skeletal muscle β‐adrenoceptor changes and oxidative metabolism in experimental chronic heart failure†

In chronic heart failure (CHF), changes in sympathetic nervous activity and skeletal muscle metabolism contribute to a limitation in the capacity for exercise. The aim of this study was to investigate the potential relationships between physical deconditioning, skeletal muscle /Ladrenoceptor (/LARj characteristics and muscle metabolic changes in rats with coronary ligation-induced experimental CHF. Muscle BAR and norepinephrine levels were assessed in rats with CHF that had been treated with propranolol at 28 mg/kg/day and compared with rats with CHF that had not been treated and those that had undergone sham operations. The soleus muscle was investigated because of its predominantly oxidative fibre-type composition. Measurements of spontaneous locomotion activity were carried out using telemetry. After 85 days, muscle energetic phosphate levels were assessed using 31 P-magnetic resonance spectroscopy. The phosphocreatine resynthesis rate was decreased in the untreated CHF rats (15 ± 3 vs 33 ± 5 mmol L-' min-' in the sham-operated rats,p p < 0.05), but this had been partially reversed in the rats given propranolol (22 ± 3 mmol L-' min-', non-significant (NS) when compared with the sham-operated rats). Spontaneous activity did not differ among the three groups of animals. Soleus /Ladrenoceptor density was decreased in rats with CHF (8.8 ± 3.0 fM/mg of protein vs 22.0 ± 7.0 fM/mg of protein in the sham-operated rats, p < 0.05) and normalized in the propranolol-treated rats (31.9 t 7.0 fM/mg of protein, NS vs the sham-operated rats; p < 0.05 vs the untreated rats with CHF). Unchanged spontaneous activity in the rats with CHF suggests that physical deconditioning could not account for the muscle metabolic changes. Changes in skeletal muscle energy metabolism were accompanied by changes in β-AR density, occurring in typically oxidative β-AR-rich muscles, reversible after β-blocker therapy and therefore suggestive of β-AR downregulation.