Reversible alterations in excitation-contraction coupling during myocardial hypertrophy in rat papillary muscle.

Abstract

To investigate the possible role of an alteration in excitation-contraction coupling in cardiac hypertrophy, we compared simultaneously recorded action potentials along with isometric or isotonic contractions of normal and hypertrophied papillary muscles. Hypertrophy was produced by renal hypertension in rats. Hypertrophied papillary muscles were taken from rats that had been hypertensive for 10 [HBP (10)] or 20 [HBP (20)] weeks. Regression of changes induced by hypertrophy was studied in rats that had been hypertensive for 10 weeks and then made normotensive for 10 weeks by removal of the ischemic kidney. Papillary muscles from age-matched, sham-operated rats [SHAM (10), SHAM (20)] were used as controls. We found that HBP (10) rats had significantly longer action potentials than SHAM (10) rats and that difference in the action potential duration recorded during isotonic and isometric contractions was significantly different from SHAM (10) and HBP (10) rats. Peak developed tension was the same in HBP (10) and SHAM (10) muscles, but the duration of isometric contraction and time-to-peak shortening were longer in HBP (10) muscles. Similarly, whereas the peak tension was the same in HBP (20) and SHAM (20) muscles, the duration of the action potential and isometric contraction, as well as the time-to-peak tension, was longer in HBP (20) muscles. The longer values for action potential duration, isometric contraction, and time-to-peak tension in HBP (20) muscles returned to SHAM values in HBP (R) muscles. The functional relationship between contraction and the action potential time course was assessed by plotting action potential duration against four parameters of contraction: peak developed tension, time-to-peak tension, time-to-half relaxation, and time-to-peak shortening. Statistical analysis of these data showed a significant correlation between action potential duration and all four parameters of contraction in SHAM (10) and SHAM (20) muscles. In contrast, HBP (10) muscles showed a significant correlation between action potential duration and only two contractile parameters, whereas action potential duration did not correlate significantly with any of the contractile parameters in HBP (20) muscles. Remarkably, in HBP (R) preparations a significant correlation was restored between action potential duration and three of the four contractile parameters. The results of this study suggest that reversible cardiac hypertrophy is associated with reversible alterations in excitation-contraction coupling. The reversibility of the mechanical and electrical alterations that accompany hypertrophy suggests, in turn, that cardiac hypertrophy is an adaptive process.