Central and primary visceral afferents to nucleus tractus solitarii may generate nitric oxide as a membrane-permeant neuronal messenger

Abstract

An anatomical basis was sought for the postulated roles of nitric oxide (NO) as a labile transcellular messenger in the dorsal vagal complex (NTS-X). The diaphorase activity of NO synthase was used as a marker of neurons in NTS-X that are presumed to convert L-arginine to L-citrulline and NO. Nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) staining patterns in the nucleus tractus solitarii (NTS) were spatially related to terminal sites of primary visceral afferents from 1) orosensory receptors (e.g., rostral-central nucleus); 2) soft palate, pharynx, larynx, and tracheobronchial tree (e.g., dorsal, intermediate, and interstitial nuclei); 3) esophagus (nucleus centralis); 4) stomach (nucleus gelatinosus); 5) hepatic and coeliac nerves (nucleus subpostrema); and 6) carotid body and baroreceptors (medial commissural and dorsal-lateral nuclei). Primary visceral afferents were identified as sources of NADPHd-stained fiber plexuses in the NTS-X based on three findings: 1) the presence of NADPHd in nodose ganglion cells with morphological features of first-order sensory relay neurons; 2) retrograde transport of Fluoro-Gold (FG) or cholera toxin B (CT-B) from NTS-X to NADPHd-positive nodose ganglion neurons; and 3) striking reductions of NADPHd-stained processes within primary vagal projection fields ipsilateral to unilateral nodose ganglionectomy. A central origin of NADPHd-stained processes in NTS-X was identified in the medial parvicellular subdivision of the paraventricular hypothalamic nucleus. We conclude that NO of peripheral and central origin may modulate viscerosensory signal processing in the NTS-X and autonomic reflex function.

Inhibitory effects of NO on carotid body: contribution of neural and endothelial nitric oxide synthase isoforms

“…The respiratory response to hypercapnia was similar in both groups of mice, suggesting that hypoxic chemosensory responses were selectively augmented in mutant mice deficient in nNOS. However, peripheral as well as central mechanisms dependent on nNOS integrity may contribute to the enhanced ventilatory responses to hypoxia observed in mutant mice (18,35). Our results suggest that NO produced by the nNOS isoform in the cat CB may inhibit the chemosensory responses to NaCN.…”

“…chemoreceptor; nitric oxide THE VENTILATORY EFFECTS of nitric oxide (NO) and the role played by nitric oxide synthase (NOS) isoforms are complex (14,18,30). In the nucleus tractus solitarii, NO plays a significant excitatory role in sustaining the ventilatory response to hypoxia (14,18,35). However, several lines of evidence indicate that NO produced within the carotid body (CB) is an inhibitory modulator of hypoxic chemoreception (2,8,20,25,34,38).…”

NADPH Oxidase Contributes to Angiotensin II Signaling in the Nucleus Tractus Solitarius

“…A third possibility is that superoxide reacts with nitric oxide (NO) to produce peroxynitrite, which nitrates tyrosine residues in channel proteins, thereby increasing L-type Ca 2ϩ channel activity (Ohkuma et al, 2001). Indeed, there is evidence that NO synthase (NOS) is present in NTS (Ruggiero et al, 1996) and that inhibition of NOS produces alterations in baroreceptor function induced by AngII (Paton et al, 2001;Zucker et al, 2004). This conclusion was reached on the basis of studies using dominant-negative inhibitors of endothelial nitric oxide synthase (eNOS), which blocked the effects of AngII on baroreceptors in rat heart-brainstem preparations (Wong et al, 2002).…”

The myth of nitric oxide in central cardiovascular control by the nucleus tractus solitarii

“…We have previously shown that NMDA receptors within the nucleus tractus solitarii (NTS) are integral to the baroreceptor reflex (12), and others have suggested that nitroxidergic mechanisms may play a role in cardiovascular control through the NTS (13)(14)(15)(16)(17). We have sought to test this hypothesis and determine if NO• released from donor compounds elicits cardiovascular responses when administered into the NTS, the primary site of termination of vagal and glossopharyngeal cardiovascular afferent nerves.…”

“…Direct evidence for the synthesis of S-nitrosothiols by the brain has also been provided by a recent report (34). The physiological relevance of nitroxidergic pathways in the NTS has been suggested by others who have shown that NOS is reduced in the NTS after removal of a nodose ganglion (14,17). Thus, vagal afferents, some of which contribute to cardiovascular reflex transmission, may have the capacity to synthesize NO•, and by implication, S-nitrosothiols.…”