Growth hormone reverses age-related cardiac myofilament dysfunction in rats

Abstract

We tested the hypotheses that aging is associated with a reduction in overall cardiac contractility and myofilament force generation that could be reversed with growth hormone (GH) replacement. Three groups of male Brown-Norway rats were studied: young (YSAL: 8 mo old, n = 13), old (OSAL: 28 mo old, n = 13), and old GH-treated (OGH: 28 mo old, n = 12; 300 μg bovine GH, twice a day for 30 days). The left ventricular (LV) pressure-volume relation was derived in isolated hearts, after which isolated trabecular muscles from these hearts were permeabilized and maximal myofilament force generation (Fmax) was measured. LV developed pressures at a LV volume of 0.3 ml were significantly depressed with age: 84 ± 6 vs. 71 ± 6 mmHg (YSAL vs. OSAL, respectively, P= 0.001) and not restored by GH (69 ± 4 mmHg). Fmaxwas reduced in the aged hearts: 47.5 ± 3.12 vs. 35.9 ± 3.03 mN/mm2 (YSAL vs. OSAL, respectively, P = 0.014) but was restored with GH replacement to 46.7 ± 3.12 mN/mm2 (OSALvs. OGH, P = 0.021). Our results suggest that cellular myofilament contractility is reduced with aging and restored with GH replacement.