Changes in myosin isoenzymes, ATPase activity, and contraction duration in rat cardiac muscle with aging can be modulated by thyroxine.

Abstract

To determine whether the relative decline in cardiac myosin isoenzyme V, with maturation continues progressively into senescence and whether thyroxine could reverse age-associated changes in the myosin isoenzyme profile and contraction, rats 2, 8, and 24 months old were treated with thyroxine, 6.4 mg/kg, for 7 days. Myosin isoenzymes, Ca 2+ -myosin ATPase activities, and isometric contractile function were measured in cardiac preparations from thyroxine-treated animals and age-matched controls. Right ventricular hypertrophy did not occur with aging in controls. Thyroxine increased right ventricular weight in each age group compared to the control group. Body weight decreased by 10% in all thyroxine-treated rats. The relative right ventricular V, isoenzyme content progressively decreased from 75 ± 1% to 54 ± 1% and 14 ± 1% in controls at 2,8, and 24 months, respectively, and was associated with a reciprocal increase in V 3 myosin isoenzyme. Ca 2+-myosin ATPase activity also progressively declined monotonically with age in the control rats from 854 ± 28 nmol Pi/mg prot/min at 2 months to 529 ± 28 nmol Pi/mg prot/min at 24 months. Thyroxine administration increased right ventricular V, at each age to 97 ± 2%, 73 ± 2%, and 59 ± 2% at 2, 8, and 24 months, respectively. A thyroxine induced increase in the Ca 1+ -myosin ATPase activity could be detected only in the 24-month-old animals. Isometric contraction duration in thin right ventricular papillary muscles increased with age from 172 ± 4 to 180 ± 5 to 225 ± 8 ms at 2, 8, and 24 months, respectively, and was markedly shortened (p<0.001) by thyroxine at each age so that the 24-month thyroxine value was less than the 2-month control. The maximum rate of force production did not change with age in controls and was increased by thyroxine at all ages. Thus, with aging from maturation to senescence, even in the absence of right ventricular hypertrophy, there is a profound monotonic decrease in percent right ventricular V, that is paralleled by a decline in Ca As the euthyroid rat matures, the percent of V, decreases while the percent of V 3 increases, l8 -25 -28 and this shift is accompanied by a decrease in the ATPase ac-

Age-related differences in the expression of proto-oncogene and contractile protein genes in response to pressure overload in the rat myocardium.

“…Expression of mRNAs encoding the SR Ca2+-ATPase and cardiac calsequestrin in the rat LV myocardium. RNA blot hybridization was carried out with cDNA clones specific for the rabbit cardiac-slow twitch skeletal SR Ca2+-ATPase (27) and canine cardiac calsequestrin (25). The SR Ca2+-ATPase cDNA probe (pCA) hybridized with an mRNA species of -4 kb.…”

“…Physiological studies of LV papillary muscle preparations have revealed that the duration of tension and the time to half-relaxation were prolonged in aged rats compared with in their younger cohort (21, 24). The prolongation of myocardial contraction has been attributed to a decline ofCa2+-activated myosin-ATPase activity, secondary to a decrease in the percentage of a-MHC or V1 isozyme (25,26). The abnormal myocardial relaxation has been thought to reflect age-related decreases in Ca2+-uptake by the SR (27,28).…”

Lack of Effect of Running Training at Two Intensities on Cardiac Myosin Isozyme Composition in Rats.

“…Furthermore, V3 exhibits a greater economy of force production than V1 [4]. Thus myosin isozyme composition is related to myocardial performance [5,6]. Furthermore, the myosin isozyme composition of ventricular muscle is developmentally, physiologically, and hormonally regulated [7].…”

Effect of long-term food restriction on cardiac mechanics

“…A number of age-associated biochemical alterations may contribute to the aging changes seen at the cellular level. In rodents, one of the most prominent biochemical changes in the aging myocardium is the shift of the myosin isozyme profile from the fast, V 1 isoform to the slow, V 3 isoform (8,15,25,34,37). This shift is involved in and/or is associated with changes in many of the physiological parameters mentioned above.…”