Lipopolysaccharide-induced hypotension is mediated by a neural pathway involving the vagus nerve, the nucleus tractus solitarius and alpha-adrenergic receptors in the preoptic anterior hypothalamic area

Dysfunctional Nucleus Tractus Solitarius: Its Crucial Role in Promoting Neuropathogentic Cascade of Alzheimer’s Dementia—A Novel Hypothesis

“…These data suggest that LPS function is mediated by the vagus nerve which conveys the signal to the NTS that in turn stimulates norepinephrine release within the POA [216]. VNS stimulates both vagal afferents and efferents [217], and neural activation of NTS enhancing the brain-derived antiinflammatory response [216,218,219]. The vagal nerve, therefore, is an important modulator of the immune system [172,220]; it controls inflammation and modulates the immune response through a 'nicotinic anti-inflammatory pathway' dependent on the alpha7-nicotinic ACh receptor [221].…”

“…Subdiaphragmatic vagotomy or abdominal perivagal lidocaine administration, or lidocaine injection into the NTS prevented the LPS action. These data suggest that LPS function is mediated by the vagus nerve which conveys the signal to the NTS that in turn stimulates norepinephrine release within the POA [216]. VNS stimulates both vagal afferents and efferents [217], and neural activation of NTS enhancing the brain-derived antiinflammatory response [216,218,219].…”

The OVLT initiates the fall in arterial pressure evoked by high dose lipopolysaccharide: Evidence that dichotomous, dose-related mechanisms mediate endotoxic hypotension

“…and arterial pressure and heart rate were recorded at 1 min intervals for 1 or 3 h. The 15 mg/kg LPS dose was selected based on evidence that it produces a prolonged hypotension and results in a mortality rate of at least 60% (Varga et al, 1998) in contrast to 1mg/kg i.v. LPS which causes little or no mortality (Rosengarten et al, 2007; Yilmaz et al, 2008a). …”

“…This hypothesis is based on evidence that LPS causes fever through a central mechanism in which the preoptic area of the hypothalamus (POA) plays a pivotal role (Blatteis et al, 2005). We found, as in the case of fever, that the fall in arterial pressure evoked by a relatively low hypotensive dose of LPS, 1 mg/kg i.v., could be prevented by microinjecting the local anesthetic lidocaine or the alpha-adrenergic receptor antagonist phentolamine into the POA of conscious or anesthetized rats (Yilmaz et al, 2008a; 2008b). Lipopolysaccharide administration also elevated extracellular norepinephrine (NE) concentrations in the POA (Villanueva et al, 2009), which suggests that LPS initially lowers arterial pressure by stimulating NE release.…”

“…In earlier studies we tested whether LPS lowers arterial pressure by activating vagus nerve afferents and found that either subdiaphragmatic vagotomy or lidocaine injection into the nucleus tractus solitarius (NTS), where vagal afferents synapse, prevented initiation of LPS hypotension completely (Yilmaz et al, 2008a). Lidocaine injection into either the OVLT or area postrema was ineffective, however.…”