IMPACT OF ACUTE HYPOXIC HYPOXIA ON THE OXIDATIVE AND NON-OXIDATIVE PHASES OF L-ARGININE METABOLISM IN MYOCARDIUM AND AORTA OF RATS IN AGE ASPECT

Abstract

Introduction. Nitric oxide is a unique factor in the regulation of vascular tone, an important component of blood and oxygen supply in humans and animals. With age, NO levels gradually decrease in hypoxia, including the so-called age-dependent diseases, primarily of the cardiovascular system.

The aim of the study – to investigate the level of stable NO metabolites, the activity of enzymes of oxidative (NO-synthase), non-oxidative (arginase) phases of L-arginine metabolism, urea content under the action of acute hypoxic hypoxia in rats of different age.

Research Methods. The experiments were performed using outbred white rats – males of two age groups: 6–8 months (young adults) and 24–26 months (old adults). Experimental animals were exposed to acute hypoxic hypoxia. Euthanasia of control and experimental rats was conducted 24 h after completion of the "launch", then blood was taken, and the heart and aorta were removed. Stable metabolites (nitrites and nitrates of nitric oxide), endothelial and inducible NO-synthase activity, urea and L-arginine content were determined.

Results and Discussion. Under hypoxia, the content of stable metabolites of nitric oxide in the myocardium of the young adult rats increased significantly compared to control, in the old adult rats – only slight increase of the nitrate level was observed (by 20 %). In older experimental animals, in contrast to young adults, the activity of eNOS in the myocardium was lower (17 %); on the other hand, the activity of inducible NO synthase exceeded its level in controls almost twice (107 %). In the blood plasma under the influence of hypoxia, the content of nitrates increased in the rats of both age groups, but to a greater extent in the old adult rats (by 68 %). In the blood plasma of old adult rats at physiological rest, the content of urea exceeded that of young adult rats (40 %). The effect of hypoxia in young adult rats caused an increase in the content of urea in the blood plasma by 69 %, though in the plasma of the old adult rats this parameter did not change and was equal to its content in young adults. The content of L-arginine was the same in the blood plasma of rats of both age groups at physiological rest and remained at the same level after hypoxia.

Conclusions. Maintaining a relatively stable level of nitrites and nitrates in the myocardium of old experimental rats, in contrast to young adults, is solely due to the increased activity of inducible NO synthase. The reason for this phenomenon may be the inhibition of eNO-synthase, which is caused by inducible NO-synthase under the conditions of profound expression by the excessive production of nitric oxide. Activation of the L-arginine non-oxidative pathway can limit NO synthesis by inhibiting iNO synthase, as well as by competing for a common substrate. The ratio between L-arginine metabolism pathways depends largely on hypoxia and the development of adaptation. After exposure to hypoxia, arginase activity decreases in young adult rats, while in the old ones – remains at same level as in corresponding control group. As for blood plasma, the increase in the level of urea in it indicates a sufficient adaptation of the body to the effects of acute hypoxia, which does not occur in older rats. Since the content of arginine in the myocardium and blood plasma of control and experimental rats of both age groups is the same and does not change under the influence of hypoxia, we can prognose a sufficient substrate supply for NO-synthase reactions.