Changes in rat ventricular isomyosins with regression of cardiac hypertrophy

Abstract

The changes in ventricular isomyosin composition and Ca2+-activated ATPase activity occurring with regression of both hypertension and cardiac hypertrophy were investigated by using polyacrylamide gel electrophoresis under nondenaturing conditions, heavy chain peptide mapping, and an enzymatic assay. Eight control male Wistar rats and 14 two-kidney, one clip (Goldblatt II) hypertensive rats were studied from the fifth week of age. At 10 weeks of age, five Goldblatt II rats and four normotensive controls were killed. Five other Goldblatt II rats underwent nephrectomy of the ischemic kidney, which resulted in subsequent normalization of blood pressure. The remaining four control, four Goldblatt II rats, and five nephrectomized rats were killed at 15 weeks of age. Both the 10- and 15-week-old hypertensive rats had a significantly higher (p<0.001) biventricular weight to body weight ratio than the age-matched controls (3.84 ± 0.76 x 10-2 vs 2.75 ± 0.25 x 10-2; 5.93 ± 2.26 x 10-2 vs 2.65 ± 0.17 x 10-2). The 15-week-old nephrectomized rats had a biventricular weight to body weight ratio (2.90 ± 0.25 x 10-2) close to that of age-matched controls and significantly lower (p<0.05) than that of age-matched hypertensive rats. In both the 10- and 15-week-old hypertensive rats left ventricular myosin Ca2+-activated ATPase was significantly lower (p<0.001) than in age-matched controls (0.44 ± 0.03 vs 0.59 ± 0.06; 0.24 ± 0.05 vs 0.48 ± 0.05). Conversely, in nephrectomized rats activity was similar to that of age-matched controls (0.46 ± 0.04) and significantly higher (p<0.001) than that of age-matched hypertensive rats. The expression of 'slow' isoenzymes of myosin V2 and V3 was evident in the hypertensive animals, which displayed a decrease of the 'fast' V1 isoenzyme. Through peptide mapping of myosin heavy chains, an additional band was found in both groups of hypertensive animals that was absent in the age-matched controls. Nephrectomized 15-week-old rats showed a ventricular isomyosin composition and peptide mapping similar to that of age-matched controls. In conclusion, with normalization of blood pressure, complete reversal of cardiac hypertrophy was achieved and the biochemical and molecular properties of left ventricular myosin were fully restored.