NITRIC-OXIDE INHIBITS NEURONAL-ACTIVITY IN THE SUPRAOPTIC NUCLEUS OF THE RAT HYPOTHALAMIC SLICES

The presence of abundant nitric oxide synthase (NOS) in magnocellular neurons of the rat hypothalamus suggests that nitric oxide (NO) may be involved in controlling the release of oxytocin and vasopressin. To t est this possibility, we examined the effect of NO-related drugs on ex tracellular discharges of 124 supraoptic nucleus (SON) neurons from sl ices of rat hypothalamus in vitro. Twenty-three (43%) of 53 neurons we re inhibited by sodium nitroprusside (SNP), a spontaneous releaser of NO, at 1-3 mM, This inhibition was prevented by preincubation of the s lices with 1 mu M hemoglobin, an inactivator of NO (n = 14), whereas h emoglobin alone enhanced neuronal activity in seven (35%) of 20 neuron s. L-Arginine (1 mM), a precursor of NO, inhibited neuronal activity i n five (36%) of 14 neurons, while D-arginine (1 mM), the inactive coun terpart of L-arginine, was ineffective (n = 12). N-omega-nitro-L-argin ine methyl ester (L-NAME, 10 mu M), an inhibitor of NOS, also enhanced neuronal activity in five (29%) of 17 neurons, while N-omega-nitro-D- arginine methyl ester (DNAME, 10 mu M), the inactive enantiomer of L-N AME, was without effect (n = 11), Together, our data show that NO exer ts predominantly an inhibitory effect on SON neurons and may serve as a negative feedback loop in controlling release of oxytocin and vasopr essin. (C) 1997 Elsevier Science Inc.