Synaptic effects of nitric oxide on enkephalinergic, GABAergic, and glutamatergic networks of the rat periaqueductal gray.

Previous studies have shown that the injection of nitric oxide (NO) donating compounds into the dorsal periaqueductal gray region of the midbrain (PAG) decreases mean arterial pressure (MAP), while the injection of NO synthase (NOS) inhibitors increases MAP. In this study we used both in-vivo and in-vitro preparations and examined the effect of a NO donor and a NOS inhibitor on MAP, membrane properties, and synaptic activities in PAG neurons. We found that: (1) Injection of the NO donor hydroxylamine (HA) into the dorsal PAG decreased MAP, while the injection of the neuronal NOS (nNOS) inhibitor, 1-(2-trifluoromethylphenyl) imidazole (TRIM) increased MAP. These responses were consistent and site-specific. (2) HA-evoked hypotensive responses were mediated by PAG neuronal activity, because they were blocked by pre-injection with gamma-amino-butyric acid (GABA). (3) HA consistently increased the rate of observable synaptic events while TRIM consistently decreased the rate of observable synaptic events. (4) Bicuculline (BIC) and naloxone (NAL) blocked HA-evoked increases in the rate of observable inhibitory synaptic events. (5) Perfusion with sodium nitroprusside (SNP) and illumination with bright light consistently elevated rates of observable synaptic events, and SNP-evoked increases of excitatory synaptic events were blocked by pretreatment with glutamic acid antagonists. (6) PAG-medullary projecting neurons exhibited similar response patterns. The results of this study suggest that: (1) NO production within the PAG is a major component of PAG-mediated cardiovascular responses. (2) The effects of NO may be mediated in part by increased presynaptic vesicular release of glutamic acid, GABA, and enkephalin.