Hydrogen sulfide as a cryogenic mediator of hypoxia-induced anapyrexia

• Published in: Neuroscience 2012-01, Vol.201, p.146-156
• Main Authors: Kwiatkoski, M, Soriano, R.N, Francescato, H.D.C, Batalhao, M.E, Coimbra, T.M, Carnio, E.C, Branco, L.G.S
• Format: Article
• Language: English
• Subjects: aminooxyacetate; Aminooxyacetic Acid - pharmacology; Analysis of Variance; Animals; AVPO; Biological and medical sciences; Body Temperature - drug effects; CBS; Cyclic AMP - metabolism; Cyclic GMP - metabolism; Dose-Response Relationship, Drug; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; H 2S; Hydrogen Sulfide - metabolism; hypothalamus; hypothermia; Hypothermia - drug therapy; Hypothermia - etiology; Hypoxia - complications; Male; Microinjections; Neurology; Nitrates - metabolism; Nitric Oxide Synthase - metabolism; Nitrites - metabolism; Preoptic Area - drug effects; Preoptic Area - metabolism; Rats; Rats, Wistar; Sulfides - pharmacology; Third Ventricle - drug effects; Third Ventricle - metabolism; Time Factors; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2011.11.030

Abstract Hypoxia causes a regulated decrease in body temperature (Tb), a response that has been aptly called anapyrexia, but the mechanisms involved are not completely understood. The roles played by nitric oxide (NO) and other neurotransmitters have been documented during hypoxia-induced anapyrexia, but no information exists with respect to hydrogen sulfide (H2 S), a gaseous molecule endogenously produced by cystathionine β-synthase (CBS). We tested the hypothesis that H2 S production is enhanced during hypoxia and that the gas acts in the anteroventral preoptic region (AVPO; the most important thermosensitive and thermointegrative region of the CNS) modulating hypoxia-induced anapyrexia. Thus, we assessed CBS and nitric oxide synthase (NOS) activities [by means of H2 S and nitrite/nitrate (NOx ) production, respectively] as well as cyclic adenosine 3′,5′-monophosphate (cAMP) and cyclic guanosine 3′,5′-monophosphate (cGMP) levels in the anteroventral third ventricle region (AV3V; where the AVPO is located) during normoxia and hypoxia. Furthermore, we evaluated the effects of pharmacological modifiers of the H2 S pathway given i.c.v. or intra-AVPO. I.c.v. or intra-AVPO microinjection of CBS inhibitor caused no change in Tb under normoxia but significantly attenuated hypoxia-induced anapyrexia. During hypoxia there were concurrent increases in H2 S production, which could be prevented by CBS inhibitor, indicating the endogenous source of the gas. cAMP concentration, but not cGMP and NOx , correlated with CBS activity. CBS inhibition increased NOS activity, whereas H2 S donor decreased NOx production. In conclusion, hypoxia activates H2 S endogenous production through the CBS-H2 S pathway in the AVPO, having a cryogenic effect. Moreover, the present data are consistent with the notion that the two gaseous molecules, H2 S and NO, play a key role in mediating the drop in Tb caused by hypoxia and that a fine-balanced interplay between NOS-NO and CBS-H2 S pathways takes place in the AVPO of rats exposed to hypoxia.