Nitroxidergic influences on cardiovascular control by NTS: a link with glutamate

Abstract

Glutamate (GLU) receptor activation, which is important in cardiovascular reflex transmission through the nucleus tractus solitarii (NTS), leads to release of nitric oxide (NO.) from central nitroxidergic neurons. Therefore, we hypothesized that GLU and NO. are linked in cardiovascular control by NTS. We first sought to determine if NO. released into NTS led to cardiovascular changes like those produced by GLU and found that the nitrosothiol S-nitrosocysteine, but not NO. itself or other NO. donors, elicited such responses in anesthetized rats. The responses were dependent on activation of soluble guanylate cyclase but, not being affected by a scavenger of NO., likely did not depend on release of NO. into the extracellular space. Responses to ionotropic GLU agonists in NTS, like those to S-nitrosocysteine, were inhibited by inhibition of soluble guanylate cyclase. Inhibition of neuronal NO. synthase (nNOS) also inhibited responses to ionotropic GLU agonists. The apparent physiologic link between GLU and NO. mechanisms in NTS was further supported by anatomical studies that demonstrated frequent association between GLU-containing nerve terminals and neurons containing nNOS. Furthermore, GLU receptors were often found on NTS neurons that were immunoreactive for nNOS. The anatomical relationships between GLU and nNOS and GLU receptors and nNOS were more pronounced in some subnuclei of NTS than in others. While seen in subnuclei that are known to receive cardiovascular afferents, the association was even more prominent in subnuclei that receive gastrointestinal afferents. These studies support a role for nitroxidergic neurons in mediating cardiovascular and other visceral reflex responses that result from release of GLU into the NTS.