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 test this possibility, we examined the effect of NO-related drugs on extracellular discharges of 124 supraoptic nucleus (SON) neurons from slices of rat hypothalamus in vitro. Twenty-three (43%) of 53 neurons were inhibited by sodium nitroprusside (SNP), a spontaneous releaser of NO, at 1-3 mM. This inhibition was prevented by preincubation of the slices with 1 microM hemoglobin, an inactivator of NO (n = 14), whereas hemoglobin alone enhanced neuronal activity in seven (35%) of 20 neurons. L-Arginine (1 mM), a precursor of NO, inhibited neuronal activity in five (36%) of 14 neurons, while D-arginine (1 mM), the inactive counterpart of L-arginine, was ineffective (n = 12). N-omega-nitro-L-arginine methyl ester (L-NAME, 10 microM), an inhibitor of NOS, also enhanced neuronal activity in five (29%) of 17 neurons, while N-omega-nitro-D-arginine methyl ester (DNAME, 10 microM), the inactive enantiomer of L-NAME, was without effect (n = 11). Together, our data show that NO exerts predominantly an inhibitory effect on SON neurons and may serve as a negative feedback loop in controlling release of oxytocin and vasopressin.