EFFECT OF HYPERTROPHY ON MECHANISMS OF RELAXATION IN ISOLATED CARDIACMYOCYTES FROM GUINEA-PIG

Modifications to cell relaxation and handling of intracellular Ca have been demonstrated in animals with cardiac cell hypertrophy leading to decompensated heart failure. A previously described model of renal hy pertension leading to cardiac cell hypertrophy in the guinea pig, prod uced using the Goldblatt 2-kidney, 1-clip technique, was used to inves tigate which of the main mechanisms causing cell relaxation (the sarco plasmic reticulum Ca-adenosinetriphosphatase and Na/Ca exchanger) are altered in hypertrophy. Relaxation upon rewarming from a rapid cooling contracture was slowed in hypertrophied (H) compared with control (C) cells. Relaxation was further slowed in H compared with C cells when Na/Ca exchange was inhibited by rewarming in a Na-free, Ca-free soluti on and slowed most markedly in H cells in the presence of 10 mM caffei ne. Hypertrophy led to greater modification of cell length relaxation in comparison with the decline in the indo-1 transient, but the force- pCa relationship in skinned muscles showed that myofilament sensitivit y was unchanged. Such results indicate that cell relaxation and Ca han dling are affected in hypertrophy, possibly involving modifications of Nai Ca exchange activity.