Аннотация:
Introduction. According to a previously proposed hypothesis, the leading role in the mechanisms of alcohol dependence development belongs to the main effector peptide of the renin-angiotensin system (RAS) – angiotensin-II (A-II). In previous experiments, it was shown that long-term administration of A-II increases the consumption of ethanol, and administration of the AT2-receptor blocker A-II PD 123,319 – reduces its, aggravating in both cases the biochemical and immunocytological disorders induced by alcoholization. Long-term blockade of AT1-receptors with losartan reduces the total fluid intake (on account of water), normalizing biochemical parameters and immune cell status.
Aim: study of the effects of a long-term decrease in the activity of key RAS enzymes – renin and angiotensin-converting enzyme (ACE), which provide A-II formation, in rats with formed alcohol dependence.
Methods. Two series of experiments were performed on 60 male rats of "Wistar" population (15 experimental and 15 control animals per series). Under conditions of free choice between water and 15% ethanol solution, animals were subcutaneously implanted with osmotic minipumps (Alzet, USA), which ensure a continuous intake of substance into the body for 7 days. During experiment, daily amounts of water and alcohol arbitrarily consumed and dynamics of immunocytological and biochemical parameters were recorded. In 1st series, rats were injected with renin inhibitor – aliskiren (7.5 mg per minipump), in 2nd series – ACE inhibitor – capoten (1.7 mg per minipump), control animals – saline.
Results. It was shown that inhibitors of renin and ACE – aliskiren and capoten influenced in different directions on alcohol consumption, respectively, decreasing or increasing it. The administration of aliskiren led to the rapid elimination of many disorders of cellular immunity caused by chronic alcoholization, while the administration of capoten, on the contrary, retained most of these disorders. Apparently, this is due to the influence of the products of alternative processing A-I – the precursor of A-II, in the formation of whiches ACE is not involved, on the genesis of immunity disorders caused by chronic alcohol consumption.
Conclusion. The data obtained indicate that changes in biochemical and immunocytological parameters induced by alcoholization are significantly and ambiguously modulated by the activity of key RAS enzymes. The decrease in the activity of renin is insignificant, and the ACE – noticeably, causes an increase in the toxic effect of alcohol on organs and tissues, mainly of the immune system. It seems important that the investigated renin and ACE inhibitors are drugs widely used in clinical practice in the treatment of cardiovascular diseases.
Ключевые слова:
alcoholic motivation, renin-angiotensin system, angiotensin-II, renin, angiotensin-converting enzyme, aliskiren, capoten, lipid peroxidation, antioxidant defense, immune cell status.