Adaptational changes of sarcomere and sarcolemma during chronic cardiac overloading in rats and in humans.
In response to increasing demand, the cardiac muscle has developed several adaptational mechanisms. Gene expression is modified in a quantitative and a qualitative way since the heart hypertrophies and since its structure changes to improve the efficiency of the contraction. The sarcomere modifications are both species- and tissue-specific. An isoenzymic shift of myosin from high adenosine triphosphatase (ATPase) activity form V-1 to low activity form V-3 occurs in all conditions in which V-1 is initially predominant, i.e., in rat (and also rabbit) ventricles and the atria of other species, including humans. It was not observed in conditions in which V-3 was predominant, as in human ventricles (and also in those of cats and pigs). Another shift from creatine kinase (CK) monomer M to CK B, the form that predominates in the fetal heart, is also observed. The sarcolemma is also modified, at least in rats. The digitalis receptor was characterized by studying the inotropic effect of the drug on an isolated heart preparation and on a purified preparation of sarcolemma with a high Na+,K(+)-ATPase activity by binding [3H]ouabain and ouabain-induced inhibition of the enzymatic activity. In hypertrophied heart, both the recovery of normal contractility after ouabain infusion and the release of previously bound ouabain infusion and the release of previously bound ouabain were slowed, as for fetal hearts. Changes in other inotropic receptors have also been reported. From a practical point of view, this means that screening of new inotropic agents has to be done on hypertrophied hearts and not, as usual, on normal tissue.
Swynghedauw
B
B
U 127-INSERM, Hôpital Lariboisière, Paris, France.
Lelièvre
L
L
Charlemagne
D
D
Chevalier
B
B
Lauer
B
B
Lompré
A M
AM
Mercadier
J J
JJ
Samuel
J L
JL
Schwartz
K
K
Rappaport
L
L
D000328:Adult; D000818:Animals; D006332:Cardiomegaly / Q000503:physiopathology*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D011247:Pregnancy; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D012508:Sarcolemma / Q000502:physiology*; D012518:Sarcomeres / Q000502:physiology*