MYOSIN ISOENZYMIC CHANGES IN SEVERAL MODELS OF RAT CARDIAC-HYPERTROPHY

The effect of chronic mechanical overloading on the isoenzymic composition of rat cardiac myosin in several experimental models was studied: aortic stenosis (AS), aortic incompetence (AI), aortocaval fistula (ACF), overload of the non-infarcted area after left coronary ligation (INF) and overload of the spontaneously hypertensive rats (SHR). Samples of the left and right ventricles were isolated from these hearts, and myosins were analyzed by electrophoresis in non-dissociating conditions. The myosin isoenzymes were called V1, V2 and V3 in order of decreasing mobility. Controls of the Wistar and Wistar Kyoto (WKY) strains were almost exclusively V1. A slow age-dependent shift toward V3 was observed in the left ventricles of adult Wistar rats, which at 30 wk of age (body wt 600 g) contained approximately 15% of this form. In all models of cardiasc hypertrophy, an isoenzymic redistribution was observed with a significant increase in V3. The level of V3 was statistically correlated with the degree of hypertrophy in the AS, (n = 11, r = 0.6, P < 0.05), the AI (n = 14, r = 0.88, P < 0.001) and the AS + AI (n = 14, r = 0.69, P < 0.01) but not in the ACF (n = 16, r = 0.46). The isoenzymic changes could account for the decreases in both myosin ATPase activity and cardiac contractility described previously in the laboratory. They also demonstrate that changes in myosin isoenzymes represent a general response of the rat heart, to chronic mechanical overloading.