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.