The economy of isometric force development, myosin isoenzyme pattern and myofibrillar ATPase activity in normal and hypothyroid rat myocardium

Abstract

Hypothyroidism was induced in Wistar-Kyoto rats by adding propylthiouracil to the drinking water (0.8 mg/ml). Initial heat, total activity-related heat, and resting heat rate were measured in left ventricular papillary muscle preparations of propylthiouracil-treated and control rats contracting isometrically at 12 beats/min (21° C), using Hill type, planar vacuum-deposited bismuth and antimony thermopiles. In the propylthiouracil preparations, relative to control, time-to-peak tension increased from 288 ± 27 (mean ± SD) to 411 ± 25 msec (P < 0.001), dp/dt(max) decreased from 38.3 ± 9.5 to 20.4 ± 3.5 g.mm-2/sec (P < 0.001), and peak developed tension decreased from 6.11 ± 1.75 to 4.64 ± 0.89 g.mm-2/sec (P < 0.05). In the propylthiouracil preparations, initial heat was significantly (P < 0.001) reduced by 27 or 43% when normalized to peak twitch tension or tension-time integral, respectively. In experiments where the papillary muscles were tetanized, the slope of the linear function of total activity-related heat versus tension-time integral was decreased by 43% (P < 0.001) in the propylthiouracil preparations, indicating an improved economy of isometric tension maintenance. The predominant myosin isoenzyme of the left ventricular wall, as well as the papillary muscle myocardium, was the V3 variety in the propylthiouracil animals, in contrast to V1 in the controls. Myofibrillar actomyosin calcium-magnesium-stimulated adenosine triphosphatase activity was significantly (P < 0.02) decreased from 55 ± 18 (control) to 31 ± 8 nmol inorganic phosphate ion/mg.min (propylthiouracil). Correspondingly, the myofibrillar myosin calcium-stimulated adenosine triphosphatase activity was also significantly (P < 0.01) decreased from 294 ± 98 (control) to 85 ± 25 nmol inorganic phosphate ion/mg.min (propylthiouracil). The results give evidence of (1) increased economy of force generation and maintenance in propylthiouracil myocardium, which is paralleled by (2) structural changes of myosin (shifts in the isoenzyme pattern), and (3) associated changes of myofibrillar adenosine triphosphatase activity. We conclude that the observed myothermal data reflect slowed crossbridge cycling in propylthiouracil myocardium, which must not necessarily be interpreted as being detrimental, in view of the increased economy of force generation.