Activation of hypothalamic neuronal nitric oxide synthase in lithium-induced diabetes insipidus rats

The expression of the neuronal nitric oxide synthase (nNOS) gene in the par aventricular (PVN) and supraoptic nuclei (SON) in rats with lithium (Li)-in duced polyuria was examined by using in situ hybridization histochemistry. The state of the thyroid axis in these rats was also examined by in situ hy bridization histochemistry for thyrotropin-releasing hormone (TRH) and thyr oid-stimulating hormone (TSH) mRNAs and radioimmunoassay for circulating th yroid hormones. Adult male Wistar rats consuming a diet that contained LiC1 (60 mmol/kg) for 4 weeks developed remarkable polyuria. The urine in the L i-treated rats was hypotonic and had a large volume and low ionic concentra tion. The nNOS mRNA in the PVN and SON was significantly increased in the L i-treated rats in comparison with that in control. The increased levels of the nNOS mRNA in the PVN and SON were confirmed by NADPH-diaphorase histoch emical staining, There were no differences of TRH mRNA in the PVN, TSH mRNA in the anterior pituitary and plasma concentrations of free T3 and free T4 between Li-treated rats and control rats. These results suggest that Li-in duced diabetes insipidus may activate nNOS in the PVN and SON without chang e of the thyroid axis. (C) 2001 Elsevier Science Ltd. All rights reserved.