Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebral ischemic preconditioning or tolerance is a powerful neuroprotective phenomenon by which a sublethal injurious stimulus renders the brain resistant to a subsequent damaging ischemic insult. We used lipopolysaccharide (LPS) as a preconditioning stimulus in a mouse model of middle cerebral artery occlusion (MCAO) to examine whether improvements in cerebrovascular function contribute to the protective effect. Administration of LPS 24 h before MCAO reduced the infarct by 68% and improved ischemic cerebral blood flow (CBF) by 114% in brain areas spared from infarction. In addition, LPS prevented the dysfunction in cerebrovascular regulation induced by MCAO, as demonstrated by normalization of the increase in CBF produced by neural activity, hypercapnia, or by the endothelium-dependent vasodilator acetylcholine. These beneficial effects of LPS were not observed in mice lacking inducible nitric oxide synthase (iNOS) or the nox2 subunit of the superoxide-producing enzyme NADPH oxidase. LPS increased reactive oxygen species and the peroxynitrite marker 3-nitrotyrosine in wild-type mice but not in nox2 nulls. The peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron (III) attenuated LPS-induced nitration and counteracted the beneficial effects of LPS on infarct volume, ischemic CBF, and vascular reactivity. Thus, LPS preserves neurovascular function and ameliorates CBF in regions of the ischemic territory at risk for infarction. This effect is mediated by peroxynitrite formed from iNOS-derived NO and nox2-derived superoxide. The data indicate that preservation of cerebrovascular function is an essential component of ischemic tolerance and suggest that combining neuroprotection and vasoprotection may be a valuable strategy for treating ischemic brain injury.
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PMID:Neurovascular protection by ischemic tolerance: role of nitric oxide and reactive oxygen species. 1761 Dec 61

Recent studies have shown that acute intermittent hypoxia (IH) induces sensory plasticity of the carotid body manifested as sensory long-term facilitation (LTF), which requires prior conditioning with chronic IH and is mediated by reactive oxygen species (ROS). The purpose of this article is to provide a brief review of chronic IH-induced sensory LTF of the carotid body, sources of ROS, mechanisms underlying sensory LTF and its functional significance. Development of sensory LTF requires conditioning with several days of chronic IH. It is completely reversible following re-oxygenation, does not depend on the severity of hypoxia used for IH conditioning, not species specific and is selectively evoked by acute repetitive hypoxia but not by repetitive hypercapnia. Sensory LTF is not associated morphological changes in the carotid body and is expressed in chronic IH treated adult but not in neonatal rat carotid bodies. Chronic IH increases ROS levels in the carotid body involving 5-HT mediated activation of NADPH oxidase-2 (NOX2) and subsequent inhibition of the mitochondrial complex I. Sensory LTF can be prevented by inhibitors of 5-HT receptors, NOX inhibitors as well as by anti-oxidants. The signaling pathways mediating the sensory LTF are summarized in the second figure. It is suggested that sensory LTF contributes to the persistent sympathetic excitation under chronic IH.
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PMID:Sensory plasticity of the carotid body: role of reactive oxygen species and physiological significance. 2162 Oct 9