SKELETAL-MUSCLE BETA-ADRENOCEPTORS AND PHOSPHATE-METABOLISM ABNORMALITIES IN HEART-FAILURE IN RATS

To investigate the mechanisms leading to skeletal muscle metabolic abn ormalities in chronic heart failure (CHF), we studied phosphate metabo lism and skeletal muscle beta-adrenoreceptors (beta-AR) in rats 12-14 wk after coronary ligation (CL). We performed P-31 magnetic resonance spectroscopy in the gastrocnemius muscle during motor activity produce d by electrical stimulation (5 Hz). The initial slope of phosphocreati ne (PCr) depletion was higher in the CL rats compared with sham-operat ed rats (P-i/PCr/time: 0.211 +/- 0.045 vs. 0.113 +/- 0.029; P < 0.05). During recovery, both PCr resynthesis rate and maximal rate of oxidat ive ATP synthesis were reduced threefold in the CL rats compared with controls (11 +/- 2 vs. 37 +/- 7 mmol . l(-1). min(-1), P < 0.04; and 2 0 +/- 3 vs. 79 +/- 18 mmol . l(-1). min(-1), P < 0.03, respectively). There were no significant differences either for the skeletal muscle d ensity (13 +/- 6 vs. 15 +/- 3 fM/mg) or for the affinity (0.244 +/- 0. 149 vs. 0.246 +/- 0.146 nM) of beta-AR between the two groups. This st udy showed that, although in moderate CHF skeletal muscle metabolic ab normalities can be demonstrated, these changes could not be explained by skeletal muscle beta-adrenergic receptor alterations in this experi mental model.