THE ROLE OF ITP-DAG REGULATORY CASCADE IN THE MECHANISM OF CARDIOPROTECTIVE EFFECT OF ADAPTATION TO STRESS

OBJECTIVE: To study the role of inositoltriphosphate-diacylglycerol (I TP-DAG) regulatory cascade in the development of adaptive stabilizatio n of structures.DESIGN: Double-blind, randomized trial. ANIMALS: Wista r male rats, 250 to 300 g. INTERVENTIONS: Adaptation to restrained str ess. Investigation of adapted animals consisted of three main steps: f irst, alpha1-adrenoreactivity of isolated heart from animals adapted t o short term stress exposure were studied. Second, the state of a1-adr enoceptors and phospholipase C activity were estimated by biochemical methods. Third, the contractile function of heart and its in vivo resi stance to acute anoxia were studied as well as the resistance of isola ted heart to ischemia reperfusion injury. All these studies were perfo rmed 15 and 30 days following the onset of adaptation to immobilizatio n stress. MAIN RESULTS: It is known that in adaptation to repeated str ess exposure, a phenomenon of adaptive stabilization of structures (Ph ASS) develops. This phenomenon manifests itself, in particular, in iso lated hearts from adapted animals as well as nuclei and cytoplasmic or ganelles of cardiomyocytes that acquire quite a high resistance to a b road spectrum of damaging factors. The present study shows that the de velopment of PhASS and its cardioprotective effects with respect to an oxia, ischemia and reperfusion are associated with an increase in posi tive 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 ef fect disappears simultaneously. A hypothesis on the important role of ITP-DAG regulatory cascade in PhASS development is put forward. CONCLU SION: ITP-DAG regulatory cascade plays an important role in the mechan ism of cardioprotective effect of adaptation to repeated stress exposu re, in particular in increased resistance of the heart to ischemia and subsequent reperfusion.