Transcriptional up‐regulation of nitric oxide synthase II by nuclear factor‐κB at rostral ventrolateral medulla in a rat mevinphos intoxication model of brain stem death

Abstract

As the origin of a 'life-and-death' signal that reflects central cardiovascular regulatory failure during brain stem death, the rostral ventrolateral medulla (RVLM) is a suitable neural substrate for mechanistic delineation of this vital phenomenon. Using a clinically relevant animal model that employed the organophosphate pesticide mevinphos (Mev) as the experimental insult, we evaluated the hypothesis that transcriptional up-regulation of nitric oxide synthase I or II (NOS I or II) gene expression by nuclear factor-κB (NF-κB) on activation of muscarinic receptors in the RVLM underlies brain stem death. In Sprague-Dawley rats maintained under propofol anaesthesia, co-microinjection of muscarinic M2R (methoctramine) or M4R (tropicamide), but not M1R (pirenzepine) or M3R (

Nitrosative Stress-Induced Disruption of Baroreflex Neural Circuits in a Rat Model of Hepatic Encephalopathy: A DTI Study

“…In addition, the high level of glutamine-derived ammonia within mitochondria reportedly brings about generation of ROS/RNS or cerebral RNA oxidation743. It should be pointed out that previous work from our laboratory16171819202122232425 emphasizes that it is nitrosative stress induced by peroxynitrite in key nuclei of the baroreflex circuit, rather than oxidative stress, that underpins defunct baroreflex-medicated sympathetic vasomotor tone, leading to brain death. This notion is again substantiated in the present study.…”

“…Nonetheless, under pathological conditions, our laboratory has demonstrated in comatose patients that irreversible loss of baroreflex-mediated sympathetic vasomotor tone is a hallmark for brain death12131415. We further identified that nitrosative stress in key nuclei of the neural circuit is the culprit for the defunct baroreflex16 in animal models of brain death16171819202122232425. Intriguingly, patients with alcoholic cirrhosis exhibit reduced baroreflex sensitivity26, and the degree of decreased HR variability is related to the severity of HE in patients with cirrhosis27.…”

Adenosine A2AR modulates cardiovascular function by activating ERK1/2 signal in the rostral ventrolateral medulla of acute myocardial ischemic rats

“…stainless steel bore to cover the anatomical boundaries of the RVLM (Chan et al, 2007). Tissue samples of the RVLM were stored at −80°C until use.…”

Hypercapnia causes cellular oxidation and nitrosation in addition to acidosis: implications for CO2chemoreceptor function and dysfunction

“…1, Rxn 2). NOS immunoreactivity has been localized in the caudal NTS (40,64,67), DMV (94), PBC (48), RVLM (7,13,44,64,95), and dorsal raphe (66,84). Microinjection of • NO donor unilaterally into the NTS in awake and unrestrained rats stimulated ventilation in both normoxia and hypoxia, whereas microinjection of NOS inhibitor into the NTS blunted the hypoxic ventilatory response (62).…”

“…The only chemosensitive region in which ONOO Ϫ activity has been measured is the RVLM; no other chemosensitive area has been investigated to my knowledge. In the RVLM, ONOO Ϫ has been implicated in fatal cardiovascular depression (7,8) and endotoxin-induced apoptosis (25). That said, it is plausible that ONOO Ϫ is synthesized in other chemosensitive areas given reports that NOS/…”