The adaptive changes in the isoenzyme pattern of myosin from hypertrophied rat myocardium as a result of pressure overload and physical training

Abstract

The distribution of cardiac myosin isoenzymes is altered as a result of pressure overload and physical training. Using polyacrylamide gel electrophoresis in sodium pyrophosphate, it was found that myosin from left ventricles of adult rats exists in three polymorphic forms, V1, V2 and V3. Cardiac hypertrophy due to renal hypertension (Goldblatt II) led to a shift of the isoenzymes towards V3, whereas swimming training resulted in an opposite redistribution. The isoenzyme V1 predominated, only traces of V2 and V3 were detectable. The changes in the isoenzyme distribution were reflected in an altered ATPase activity of myofibrils. In a representative sample of the Goldblatt rats, the activity was reduced by 11%, and the swimming training led to an increase by 10%. Changes in myofibrillar ATPase can, therefore, be traced to alterations in the isoenzyme pattern of myosin. The polymorphism of myosin has a two-faced aspect as regards cardiac performance. For example, a shift towards V3 is expected to increase the economy for tension development during isovolumetric contraction at the expense of a reduced maximum speed of ventricular contraction.

Physiologic cardiac hypertrophy corrects contractile protein abnormalities associated with pathologic hypertrophy in rats.

“…As in numerous other investigations (2,3,8,9 and others) this study documents the sensitivity of the pyrophosphate gel technique in detecting changes in isoenzyme distribution in rat cardiac myosin. When myosins with lower ATPase activities are studied, more sensitive approaches, such as the use of monoclonal antiisoenzyme antibodies appear to be required (11), but this has not been necessary with rat cardiac myosin.…”

“…On the other hand, it has been observed in the rat that physiologic loads such as chronic exercise, which result in cardiac hypertrophy in the rat, may increase contractile performance (1), contractile protein ATPase activity (1), and a shift to even a greater predominance of the V1 myosin isoenzyme (3).…”

Myosin heavy chain messenger RNA and protein isoform transitions during cardiac hypertrophy. Interaction between hemodynamic and thyroid hormone-induced signals.

“…It has been shown that many other pathophysiological states, including exercise (52,53), diabetes (54,55), starvation (56), high carbohydrate diet (56), adrenalectomy (56), dwarfism (57), and gonadectomy (58), can also modulate the cardiac MHC isozyme distribution. It remains to be seen whether these stimuli act independently on the expression of the MHC genes or whether their effects are mediated by a common biochemical signal.…”

Developmental and hormonal regulation of sarcomeric myosin heavy chain gene family.

“…It has been shown that other physiologic and hormonal factors, such as exercise, 61 denervation, 8 hemodynamic overload, 41 a high carbohydrate diet, 12 insulin," growth hormone, 35 glucocorticoid, 12 and sex steroids 13 can also modulate MHC isoform expression in cardiac and skeletal muscles. It remains to be seen whether these various stimuli act independently on the expression of the MHC genes or whether their effects are mediated by a common final biochemical signal.…”