title: Chronic cardiac reactions. IV. Effect of drugs and altered functional loads on cardiac energetics as inferred from myofibrillar ATPase and the myosin isoenzyme population.
abstract: A major determinant of myocardial energetics is the ATPase activity of myofibrils. In order to account for chronic changes in myofibrillar ATPase, the state equation of the intertropomyosin-interaction model of Tawada et al. was extended by introducing the rates of cross-bridge cycling of myofibrils composed of V-1 or V-3 and the concentration of the myosin isoenzymes. Cross-bridge cycling rates of 1.0 or 0.7 were derived for myofibrils composed of V-1 or V-3, respectively. Ca2+ responsiveness and positive co-operativity were not significantly affected by the myosin isoenzymes. Redistribution of the myosin isoenzyme population and thus altered myocardial energetics was observed following administration of various drugs and as a result of different functional loads. Besides thyroid hormones, catecholamines had a marked influence on myosin. Reducing the adrenergic drive by administration of atenolol, guanethidine or reserpine led to a shift in the direction of V-3. Since serum T3 levels were not significantly reduced by these interventions, the drugs act most probably at the organ level. The functional states responsible for the increase in the proportion of V-3 (pressure load, intermittent feeding, schedule-induced stress) also did not affect circulating T3 in a manner that could entirely explain the redistribution. Hypertrophy-induced dilution of sympathetic nerve fibres or reduced adrenergic responsiveness most likely play a role in the redistribution. An increase in the proportion of V-1 was observed following swimming exercise but not, however, after spontaneous or enforced running. In the swim-exercised rats, T3 was markedly reduced. Thus, the trigger reactions linked most probably to the high adrenergic drive during swimming have to overcome the lower T3 level. It is concluded that myocardial energetics can be decisively altered by a variety of drugs and functional loads, whereby the trigger reactions leading to an altered gene expression of myosin cannot be accounted for entirely by altered circulating T3 but most probably involve the adrenergic system.
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D006973:Hypertension / Q000503:physiopathology*; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D009210:Myofibrils / Q000201:enzymology*; D009218:Myosins / Q000378:metabolism*; D005082:Physical Exertion; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D014284:Triiodothyronine / Q000097:blood / Q000494:pharmacology
chemical_list: D007527:Isoenzymes; D014284:Triiodothyronine; D000251:Adenosine Triphosphatases; D009218:Myosins