[The limitation of acute hypotension and hyperactivation of the vascular endothelium in rats with an experimental myocardial infarct by using preliminary adaptation to physical load]. / Ogranichenie ostroi gipotenzii i giperaktivatsii éndoteliia sosudov krys pri éksperimental'nom infarkte miokarda s pomoshch'iu predvaritel'noi adaptatsii k fizicheskoi nagruzke.

Adaptation to swimming exercise was shown to increase the endothelium-dependent relaxation of the rat aorta, leaving the BP unaffected. In experimental myocardial infarction, the adaptation limited the BP fall and completely prevented an excessive suppression of norepinephrine-induced contractions of the aorta. An adaptation to exercise seems to be an efficient protective factor in pathological conditions involving the NO overproduction and endothelial hyperactivation.

[The effect of adaptation to a physical load on the endothelium-mediated reactions of isolated vessels and NO production in rats]. / Vliianie adaptatsii k fizicheskoi nagruzke na éndoteliioposredovannye reaktsii izolirovannykh sosudov i produktsiiu NO u krys.

Adaptation to exercise exerts a beneficial therapeutic and protective effect in several cardiovascular diseases many of which are characterized by disorders of endothelium-dependent vascular responses. To evaluate a possible role of functional condition of the endothelium in protective effects of adaptation to exercise we studied the effect of such adaptation on endothelium-dependent constrictor and dilator responses of the isolated rat aorta and on nitric oxide (NO) production in the organism. It was shown that adaptation to exercise (swimming) increased the suppression by the endothelium of constrictor responses to norepinephrine and potentiated the endothelium-dependent relaxation to acetylcholine. Furthermore adaptation to exercise considerably increased the NO production in the heart, liver, spleen, kidney and intestine as assayed by the method of electron paramagnetic resonance. We suggest that the adaptive increase in synthesis and accumulation of NO in the organism may underlie the protective effect of dosed physical training in diseases attended by disturbance of the functional condition of vascular endothelium.

The role of hsp70 and IP3-DAG mechanism in the adaptive stabilization of structures and heart protection.

This study has shown that the maximal activation of the IP3-DAG regulatory circuit is observed on the 14th day of adaptation to repeated stresses. This activation is characterized by increased activity of phospholipase C and of the positive inotropic response of isolated heart to an alpha-agonist. Simultaneously, this activation is accompanied by the accumulation of five heat shock protein 70 (hsp70) isoforms. The IP3-DAG circuit activation and the hsp70 accumulation are accompanied by a significant increase in the cardiac resistance to post-ischemic reperfusion, as evidenced by a considerable decrease in the contracture, arrhythmias and the creatine kinase release into the perfusate. Continuation of the adaptation to repeated stresses for 28 days leads to complete reversal of the observed shifts.

Physical training limits the fall of blood pressure and the endothelium overactivation in acute myocardial infarction.

Physical training (PT) is beneficial in cardiovascular diseases associated with NO deficiency such as coronary disease, hypertension, etc. However, it is not known whether PT can also prevent pathological conditions associated with excess NO and fall of blood pressure (BP) such as acute myocardial infarction (AMI). The aim was to compare the effect of AMI on BP and functional state of the endothelium in rats trained by swimming and in untrained animals. After AMI, BP fell from 110 +/- 2 to 74 +/- 4 mm Hg (p < 0.05), the endothelium-dependent relaxation increased from 37 +/- 4 to 66 +/- 6% (p < 0.05) and the extent of contraction suppression by the endothelium was significantly greater than in the controls. PT itself increased the endothelium-dependent relaxation of rat aorta but left BP unaffected. PT limited the AMI-induced fall of BP to 87 +/- 3 mm Hg, the endothelium- dependent relaxation to 53 +/- 4% and prevented the hyporesponsiveness of the aorta to norepinephrine. We suggest that the protective effect of PT is related to inhibition of inducible NO synthase by a negative feedback mechanism.

Stress-induced arrhythmic disease of the heart--Part I.

This review deals with the following principal concepts: (1) Heart injuries in single severe stress episodes manifested primarily in disturbances of membrane lipid bilayer, sarcolemmal Na, K-pump, and sarcoplasmic Ca-pump with concurrent limited disturbances of the heart energy supply, namely, of the creatine kinase and glycolysis systems. These disturbances cause small focal myocardial lesions and reduce cardiac electrical stability: the fibrillation threshold falls and ectopic activity increases. In repeated stress, this damage, localized mainly in the richly innervated conduction system, accumulates to cause even more pronounced disturbances of electrical stability and severe arrhythmias. (2) Severe stress and beta-adrenergic effects on the heart regularly result in coronary vasodilation and increased coronary blood flow. However, the entire primary complex of stress-induced injuries and disturbances of the heart's electrical stability occurs despite the increased coronary blood flow. Thus, beta-adrenergic stress-induced injuries may indeed develop as primary stress damage to cardiomyocytes without any relation to ischemia. (3) The main factor determining high vulnerability or, on the contrary, resistance of the heart to stress is the state of stress-limiting systems, namely, the opioidergic, GABAergic, cholinergic, adenosinergic, and other systems. Activation of these systems by adaptation to repeated stress or other factors prevents serious injuries to the heart in severe stress. Conversely, genetically determined or acquired dysfunction of these systems predisposes to severe arrhythmias and sudden death. Thus, in stress-induced arrhythmic disease as well as in ischemic heart disease, the main pathogenetic links are outside the heart, but they differ from those observed in ischemia. (4) The clinical picture of stress-induced arrhythmic disease, that is, alterations in electrocardiogram, coronarogram, and patient responses to stress, physical loads, and tranquilizers differ, as do pathologic alterations in the heart. These differences are summarized at the end of this review.