Mechanism of physiologic versus pathologic ventricular hypertrophy process: Enhanced or depressed myosin ATPase activity and contractility governed by type, degree and duration of inciting stress

Abstract

Types of hypertrophy, such as the normal development of the left ventricle of new-born lambs, induction of hypertrophy following administration of subhypertensive doses of norepinephrine, and hypertrophy where moderate pulmonic stenosis is the inciting stimulus, are all of a physiologic nature, i.e., cardiac function is elevated and K+ stimulated myosin ATPase activity is increased. The K+/EDTA stimulated myosin ATPase activity, used as an index of physiologic versus pathologic hypertrophy, may reflect alterations in myosin heavy chains since a large amount of light chains are in the dissociated state with this kinetic system. In experimental conditions where light-chain deficient-myosin was employed there was no corresponding decrease in myosin ATPase activity with the dissociation of light chains, irrespective of the cation activator utilized; there was however a decrease in the enzymatic activity of actomyosin with the loss of light chains. Furthermore, this decrease in actomyosin ATPase activity was partially restored with the reassociation of light chains with light-chain-deficient-myosin. Where excessive hypertrophy occurred, e.g., with moderate pulmonic stenosis, where the right ventricular free wall weight increased 100%, there was a decrease in cAMP content. This may result from the subsequent decrease in stress per sarcomere following massive hypertrophy. Where there was a lesser degree of hypertrophy, e.g., with mild pulmonic stenosis, creating a transitory 30% increase in right ventricular free wall weight, there was no subsequent decrease in cAMP content.