THE ACTIVITY OF NO-SYNTHASES IN THE BRAIN, MYOCARDIUM AND SKELETAL MUSCLES OF OBESE RATS AND THE INFLUENCE OF LONG-TERM TREATMENT WITH INTRANASAL INSULIN

Background. The abnormalities of micro- and macrocirculation in obesity are associated with the changes in the activity of NO-synthases, the enzymes catalyzing synthesis of endogenous NO. However, in experimental obesity they are not well understood. There are no data on the influence of long-term treatment with intranasally administered insulin (I-I) that is used for the treatment of pre-diabetic states on NO-synthase activity. Objective. The aim of this work was to study the activity of NO-synthases in the tissues of rats with obesity induced by high- fat diet and the influence of long-term I-I treatment on them. Design and methods. To induce the obesity, Wistar male rats received a high-fat diet during 4 months. The I-I treatment was started on the 60^th day of the diet, and carried out for two months at a daily dose 0.48 IU/rat. The activity of total, neuronal and endothelial isoforms of NO-synthase in the brain, myocardium and skeletal muscles was evaluated. Results. It was shown that in the myocardium and skeletal muscles of obese rats the activity of total and endothelial NO-synthases was decreased, and in the brain it has not significantly changed. The treatment of obese rats with II resulted in partial or complete restoration of the activity of total and endothelial NO-synthases in the myocardium and skeletal muscles, and caused an increase of NO-synthase activity in the brain above this level in control. Conclusion. Summing up, long-term I-I treatment restores insulin signaling system in the brain and positively affect the NO-synthase system in CNS and periphery, attenuated in the obesity, which can lead to improved blood circulation and to prevent the development of dysfunctions of the nervous, the cardiovascular and other systems.

NO-синтаза, ожирение, мозг, миокард, скелетные мышцы, NO-synthase, obesity, brain, myocardium, skeletal muscle

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