NITRIC-OXIDE MODULATES THE RELEASE OF VASOPRESSIN FROM RAT HYPOTHALAMIC EXPLANTS

The enzyme nitric oxide (NO) synthase is present in the paraventricula r nucleus, while nitric oxide has recently been shown to inhibit the s timulated release of corticotrophin-releasing hormone (CRH) in vitro. Thus the possible role of NO in regulating, vasopressin (AVP), which a lso plays an important role in pituitary-adrenal activity, has been in vestigated. The effects were studied of the NO donors, L-arginine, syd nonimine-1 (SIN-1) and sodium nitroprusside, on both the basal and sti mulated release of AVP, employing a previously validated system. Rat h ypothalami were incubated in either medium alone or medium containing the test substances and hormone release was measured by RIA. The effec t of L-arginine in the presence of the NO synthase inhibitor, L-NMMA, was also investigated. L-arginine reduced KCl-evoked AVP release; this effect was reversed by L-NMMA and reduced by the addition of ferrous human Hb. Similarly, SIN-1 and sodium nitroprusside attenuated KCl-evo ked AVP release. L-arginine also reduced IL-1beta-stimulated AVP relea se. NO appears to directly and specifically inhibit the stimulated rel ease of AVP from rat hypothalamic explants in vitro, similar to its ef fects on CRH. These findings provide further evidence that NO may be i nvolved in neuroendocrine regulation.