The Neuronal Nitric Oxide Synthase Immunoreactive Neurons Of Brain And Nitric Oxide Of Serum In Diabetic Rats

PURPOSES: Our experiment was to discuss the role of nitric oxide in the development of diabetes mellitus by observing the changes of neuronal nitric oxide synthase (nNOS) immunoreactive (nNOS-ir) neurons in some cerebral nucleus and that of serum glucose and serum nitric oxide in streptozotocin (STZ)-induced diabetic rats. METHODS: 72 SD rats were divided randomly into 4 groups, each contained 18 rats. The control group was treated with normal saline (NS) intraperitoneal (i.p.) administration every day. The other 3 groups were first established STZ-induced diabetic rats, then 晈ere treated separately with NS (DM+NS group), Nω-nitro- L-arginine ( DM +L-NA group) and L-Glutamic acid monoammonium salt (DM+MSG group) i.p. administration every day. At the end of 2,7 and 12 week, the equal number of rats in every group was sacrificed (n=6 each time). The number of nNOS-ir neurons in paraventricular hypothalamic nucleus (PVN), supraoptic nucleus (SON) and caudate putamen (CPu) were counted and then quantitatively analysed. The changes of serum glucose and serum nitric oxide at every period were also analysed. RESULTS: (I) The number of nNOS-ir neurons in PVN and SON of all 3 diabetic group (DM+NS.. DM+L-NA and DM+MSG group) remained normal in diabetic early stage(2 weeks); but in diabetic middle stage (7 weeks), the number of nNOS-ir neurons in PVN and SON of all 3 diabetic groups significantly increased; in diabetic late stage( 12 weeks), the number of nNOS-ir neurons in DM+NS group had still significant difference with that of the control. (2) The number of nNOS-ir neurons in CPu of all 3 diabetic groups (DM+NS~ DM+L-NA and DM+MSG group) remained normal level in the whole experimental stage. (3) The serum nitric oxide of all 3 diabetic groups increased significantly in diabetic early stage, then decreased to normal level in diabetic middle and late stages. CONCLUSIONS: (1) The number of nNOS-ir neurons in PVN and SON increased significantly in diabetic middle and late stage, which implied that the changes of nNOS activity in PVN and SON may be related to the changes of cerebral neuroendocrine and adrenal activity during diabetes. (2) The number of nNOS-ir neurons in CPu remained normal levels in whole diabetic duration, which suggested that nNOS activity in CPu may be relatively stable during diabetes. (3) The serum nitric oxide changed with the diabetic duration, serum nitric oxide mey be regarded as one of the subsidiary diadynamic criteria of diabetic stages after the final diagnosis of diabetes.