Myosin Synthesis and Degradation during Development of Cardiac Hypertrophy in the Rabbit

Abstract

Metabolism of left ventricular myosin was studied in rabbits (2.7-3.2 kg) following banding of the ascending aorta (65% occlusion). In 26 rabbits the incorporation of amino acid into myosin was determined 2, 3, 4, 9, and 15 days after either stenosis or sham operation by injecting 3 H-lysine (0.5 mc/kg) 4 hours before the animals were killed. In 32 rabbits the same dose of 3 H-lysine was injected 24 hours before surgery, and disappearance of isotope from myosin was measured by killing the rabbits after 3, 5, 7, 10, or 16 days. Specific radioactivity of free lysine, myosin, and total proteins was determined in left ventricular samples from each animal. The experimental results indicate that: (1) left ventricular peak systolic pressure increased from 97 to 163 mm Hg; (2) the ratio of left ventricular weight to body weight increased about 16% (3) disappearance of free 3 H-lysine was similar in rabbits with aortic stenosis and those with sham operations; (4) after the second day myosin synthesis was greater in rabbits with aortic coarctations, reaching a maximum increase of 117% on the tenth day; (5) synthesis of left ventricular total proteins also reached a maximum of about 56% on the tenth day; (6) the decrease in specific radioactivity of myosin in rabbits with aortic coarctation was slower than it was in sham-operated animals. The experimental results were analyzed by a computerized simulation of myosin metabolism which allowed the rate constant for myosin degradation to be calculated on successive days after coarctation. The best fit to the observed changes in myosin content was obtained when degradation was increased with the increase in synthesis; when degradation was assumed to be unchanged from sham-operated animals or was decreased, myosin content was overestimated. Moreover, these calculations showed that decay in specific radioactivity of labeled myosin was affected very little even by a large (hundredfold) decrease in degradation. It is concluded that the increased myosin content during development of cardiac hypertrophy is primarily a consequence of increased synthesis.