The role of ITP-DAG regulatory cascade in the mechanism of cardioprotective effect of adaptation to stress
Meerson, F.Z.; Kopylov, Y.N.; Golubeva LYu
Canadian Journal of Cardiology 10(1): 137-147
1994
ISSN/ISBN: 0828-282X PMID: 8111667 Document Number: 423109
Objective: To study the role of inositoltriphosphate-diacylglycerol (ITP-DAG) regulatory cascade in the development of adaptive stabilization of structures. Design: Double-blind, randomized trial. Animals: Wistar male rats, 250 to 300 g. Interventions: Adaptation to restrained stress. Investigation of adapted animals consisted of three main steps: first, alpha-1-adrenoreactivity of isolated heart from animals adapted to short term stress exposure were studied. Second, the state of alpha-1-adrenoceptors and phospholipase C activity were estimated by biochemical methods. Third, the contractile function of heart and its in vivo resistance to acute anoxia were studied as well as the resistance of isolated heart to ischemia reperfusion injury. All these studies were performed 15 and 30 days following the onset of adaptation to immobilization stress. Main Results: It is known that in adaptation to repeated stress exposure, a phenomenon of adaptive stabilization of structures (PhASS) develops. This phenomenon manifests itself, in particular, in isolated hearts from adapted animals as well as nuclei and cytoplasmic organelles of cardiomyocytes that acquire quite a high resistance to a broad spectrum of damaging factors. The present study shows that the development of PhASS and its cardioprotective effects with respect to anoxia, ischemia and reperfusion are associated with an increase in positive inotropic effect of selective alpha-agonist phenylephrine and an activation of myocardial phospholipase C. In long term adaptation both these alterations disappear and the PhASS-induced cardioprotective effect disappears simultaneously. A hypothesis on the important role of ITP-DAG regulatory cascade in PhASS development is put forward. Conclusions: ITP-DAG regulatory cascade plays an important role in the mechanism of cardioprotective effect of adaptation to repeated stress exposure, in particular in increased resistance of the heart to ischemia and subsequent reperfusion.