Effect of hypertrophy on mechanisms of relaxation in isolated cardiac myocytes 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 hypertension leading to cardiac cell hypertrophy in the guinea pig, produced using the Goldblatt 2-kidney, 1-clip technique, was used to investigate which of the main mechanisms causing cell relaxation (the sarcoplasmic 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 solution and slowed most markedly in H cells in the presence of 10 mM caffeine. 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 sensitivity was unchanged. Such results indicate that cell relaxation and Ca handling are affected in hypertrophy, possibly involving modifications of Na/Ca exchange activity.
Department of Cardiac Medicine, National Heart and Lung Institute University of London, United Kingdom.
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D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D006332:Cardiomegaly / Q000503:physiopathology*; D002478:Cells, Cultured; D005456:Fluorescent Dyes; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D066298:In Vitro Techniques; D007211:Indoles; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D012016:Reference Values; D013696:Temperature; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D005456:Fluorescent Dyes; D007211:Indoles; D013729:Terpenes; D002110:Caffeine; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; C048960:indo-1; D002118:Calcium