Effects of nitric oxide on stimulated release of norepinephrine from female rat hypothalamic slices

Norepinephrine (NE) is an important neurotransmitter involved in ovarian steroid hormone regulation of female reproductive function in rats. Nitric oxide (NO) has also been suggested to be an essential mediator of gonadotropin-releasing hormone release and of lordosis behavior of female rats. These studies used a superfusion system to investigate the hypothesis that NO regulates [H-3]NE release in the preoptic area (POA) and hypothalamus (HYP), brain regions that mediate ovarian steroid effects on reproductive function. The NO synthase inhibitors N-nitro-L-arginine and N-G-nitro-L-arginine methyl ester did not modify either basal or N-methyl-D-aspartate (NMDA)-stimulated NE release in either brain region of ovariectomized, hormone-treated or control animals. The NO precursor L-arginine (L-AIS) reduced NMDA-stimulated NE release in POA but had no effect on KCl- or electrically-stimulated release. L-Arg did not influence basal or evoked release of [H-3]NE from HYP slices. Sodium nitroprusside (SNP), a NO-generating compound, blocked the release of NE in response to NMDA stimulation but not in response to KCl or electrical stimulation. Thus, SNP is probably reducing NE release by acting as an NMDA antagonist rather than via NO production. There was a tendency for administration of both estrogen and progesterone to ovariectomized females to facilitate NMDA-stimulated NE release, particularly in the POA. Our data suggest that NO does not mediate basal or NMDA-stimulated NE release in rat POA and HYP. Therefore, NO regulation of lordosis behavior and gonadotropin release in female rats is probably not exerted at the level of NE release.