Tez özetleri Astronomi ve Uzay Bilimleri Anabilim Dalı

Relationship of Nitric Oxide and Leptin on the Cerebral Blood Flow in Diabetic Rats

Leptin is a 16 kDa polypeptide hormone of cytokin family which is encoded by the obese (ob) gene, secreted from fatty tissue essentially. The best known function of leptin is to regulate energy intake and energy expenditure.

Nitric oxide (NO) is a very important versatile signaling molecule in biological systems. It plays a significant role in a variety of physiologic and pathologic processes including neuronal transport in brain, regulation of blood pressure and digestive system, vascular system, platelet aggregation, cytotoxicity, hypertension, diabetes and atherosclerosis.

Diabetes is a syndrome characterized by hyperglycemia and glycosuria and resulting from low levels of hormone insulin, which can be resulted in ketoacidosis and coma when not treated.

In this study, relationship between leptin and NO was investigated in diabetic and non-diabetic rats by employing leptin and L-N^G-nitroarginine methyl ester (L-NAME), a non-specific NO inhibitor. How this relationship affects brain blood flow and blood pressure was revealed in rats on the basis of nitric oxide synthase (NOS) distribution.

48 male Wistar albino rats (250–300 g) of three months old were divided into eight groups forming four diabetic and four non-diabetic groups, each including six individuals. Animals received single dose of physiologic saline solution (PSS), L-NAME (10 mg/kg), leptin (50 µg/kg) and L-NAME (10 mg/kg)+leptin (50 µg/kg) intravenously (iv) under anaesthesia. Brain blood flow, arterial blood pressure and heart rate of the animals were recorded during the experiment. Serum nitrit/nitrate andd leptin levels were measured biochemically in blood samples from the animals at the end of experiment period. In addition, endothelial NOS (eNOS) and neuronal NOS (nNOS) distributions in cerebral cortex were immunohistochemically examined.

A significant difference was observed in blood flow in non-diabetic animals which were administered only leptin, while diabetic identicals did not show such a difference. In non-diabetic group receiving leptin 15 minutes after L-NAME application, leptin caused also a marked difference in blood flow in spite of L-NAME impact. However, leptin did not exhibit such an effect in diabetic rats. Average arterial blood pressure was higher both in diabetic and non-diabetic rats given L-NAME and L-NAME + Leptin when compared to values of both their relevant controls and the control group in the same time period. Average arterial blood pressure was declined by the initial point; however, arterial blood pressure values were not significant in comparison with the values of diabetic and non-diabetic control animals. Heart rates of non-diabetics were reduced by L-NAME application, significantly.

nNOS reaction was intense in diabetic rats receiving leptin, whereas it was weak in non-diabetics. In L-NAME groups, non-diabetic rats did not display either eNOS nor nNOS reaction, but a weak reaction was present in diabetic individuals. Non-diabetic L-NAME+Leptin group possessed no eNOS and nNOS reaction, while diabetic identicals showed similar eNOS and nNOS reaction to that of the intact control group.

Although serum leptin levels exhibited insignificant changes in all groups, diabetic L-NAME+leptin group was of higher levels, being significant when compared to the diabetic controls. Moreover, serum leptin levels of diabetic rats were significantly lower than those of non-diabetics.

In conclusion, this study in which effect of leptin on blood flow and pressure, and heart rate was investigated in presence and absence of NO reveals that leptin affects NO production in cerebral cortex of both diabetic and non-diabetic rats, and leptin uses NO as mediator in its physiologic functions, although NO synthesis is inhibited by L-NAME.