UP-REGULATION OF NITRIC-OXIDE SYNTHASE (NOS) GENE-EXPRESSION TOGETHERWITH NOS ACTIVITY IN THE RAT HYPOTHALAMOHYPOPHYSEAL SYSTEM AFTER CHRONIC SALT LOADING - EVIDENCE OF A NEUROMODULATORY ROLE OF NITRIC-OXIDE IN ARGININE-VASOPRESSIN AND OXYTOCIN SECRETION

Chronic salt loading up-regulated the expression of neuronal nitric ox ide synthase (NOS) mRNA in the supraoptic nucleus (SON) and paraventri cular nucleus (PVN) of the hypothalamus with a concomitant tent increa se in NOS activity in the posterior pituitary. Once daily ip injection of N-omega-nitroarginine (N-Arg), a NOS inhibitor, significantly inhi bited NOS activity in the posterior pituitary in a dose-dependent mann er, but did not influence NOS mRNA levels. Two percent salt loading fo r 3 or 4 days significantly depleted the contents of both arginine vas opressin (AVP) and oxytocin (OT) in the posterior pituitary, and simul taneous treatment with daily injections of N-Arg at a dose of 10 mg/kg significantly enhanced the depletion of both AVP and OT. This effect was dose dependent and paralleled the inhibition of NOS activity in th e posterior pituitary. N-Arg treatment had no effect on the levels of both AVP and OT transcripts in PVN or SON. These results suggest that NOS gene expression in the SON and PVN of the rat hypothalamus is incr eased during hyperosmotic stimulation and suggest a neuromodulatory ro le for NO in the rat hypothalamo-hypophysial system as an inhibitory r egulator of AVP and OT secretion.