Association of decreased myocardial β-receptors and chronotropic response to isoproterenol and exercise in pigs following chronic dynamic exercise

Abstract

The effects of chronic dynamic exercise on myocardial β-adrenergic and muscarinic cholinergic receptors and chronotropic sensitivity to isoproterenol were studied in 5 Yucatan miniswine. Right atrial and left ventricular biopsies, heart rate responses to isoproterenol, and maximal exercise treadmill testing were obtained before and after 10-19 weeks of treadmill running. Radioligand studies using 125I-iodocyanopindolol (ICYP) and 3H-quinuclidinyl benzilate (QNB) were used to determine the number of β-adrenergic and muscarinic cholinergic receptors. Maximal oxygen consumption increased from 52 ± 5 to 65 ± 7 ml/kg/min (mean ± SD; p < 0.02), maximal workload from 530 ± 111 to 1,074 ± 179 KPM/min (p < 0.01), resting heart rate decreased from 91 ± 13 to 62 ± 4 beats/min (p < 0.01), heart rate at 75% of pretraining maximal workload decreased from 253 ± 15 to 196 ± 12 beats/min (p < 0.01), and maximal exercise heart rate decreased from 273 ± 6 to 254 ± 9 beats/min (p < 0.01). Decreased heart rate responsiveness to adrenergic stimulation was observed following chronic exercise. Maximal isoproterenol-stimulated heart rate decreased from 225 ± 13 to 185 ± 28 beats/min (p < 0.05) and the slope of the isoproterenol dose-response relation decreased from 63 ± 16 to 40 ± 16 (p < 0.05). Radioligand studies revealed a decrease in β-receptor number in the right atrium following chronic exercise (61 ± 9 vs. 34 ± 8 fmol/mg; p < 0.02), but receptor number in membranes from the left ventricle did not change (60 ± 9 vs. 62 ± 4 fmol/mg). There was no change in muscarinic cholinergic receptor number in right atrial membranes following the training period (204 ± 73 vs. 230 ± 92 fmol/mg). Thus, chronic dynamic exercise results in down-regulation of β-adrenergic receptors in the right atrium and is associated with reduced chronotropic responsiveness to exercise and isoproterenol stimulation.