title: Cryogenic role of central endogenous hydrogen sulfide in the rat model of endotoxic shock.
abstract: Thermoregulatory responses to lipopolysaccharide (LPS) are affected by modulators that increase (propyretic) or decrease (cryogenic) body temperature (Tb). We tested the hypothesis that central hydrogen sulfide (H2S) acts as a thermoregulatory modulator and that H2S production in the anteroventral preoptic region of the hypothalamus (AVPO) is increased during hypothermia and decreased during fever induced by bacterial lipopolysaccharide (LPS, 2.5mg/kg i.p.) in rats kept at an ambient temperature of 25°C. Deep Tb was recorded before and after pharmacological inhibition of the enzyme cystathionine β-synthase (CBS - responsible for H2S endogenous production in the brain) combined or not with LPS administration. To further investigate the mechanisms responsible for these thermoregulatory adjustments, we also measured prostaglandin D2(PGD2) production in the AVPO. LPS caused typical hypothermia followed by fever. Levels of AVPO H2S were significantly increased during hypothermia when compared to both euthermic and febrile rats. Intracerebroventricular (icv) microinjection of aminooxyacetate (AOA, a CBS inhibitor; 100 pmol) neither affected Tb nor basal PGD2production during euthermia. In LPS-treated rats, AOA caused increased Tb values during hypothermia, along with enhanced PGD2production. We conclude that the gaseous messenger H2S modulates hypothermia during endotoxic shock, acting as a cryogenic molecule.
authors: Medical School of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, São Paulo, Brazil.
authors: Rodrigo A R
authors: RA
authors: Fernández
authors: Division of Physiology and Biophysics, Department of Basic Life Sciences, Federal University of Juiz de Fora, 35020-220 Governador Valadares, MG, Brazil.
authors: Renato N
authors: RN
authors: Soriano
authors: Medical School of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, São Paulo, Brazil.
authors: Heloísa D C
authors: HD
authors: Francescato
authors: Dental School of Ribeirão Preto, University of São Paulo, 14040-904 Ribeirão Preto, São Paulo, Brazil.
authors: João P
authors: JP
authors: Sabino
authors: Medical School of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, São Paulo, Brazil.
authors: Terezila M
authors: TM
authors: Coimbra
authors: Dental School of Ribeirão Preto, University of São Paulo, 14040-904 Ribeirão Preto, São Paulo, Brazil. Electronic address: branco@forp.usp.br.
authors: Luiz G S
authors: LG
authors: Branco
mesh_terms: D000625:Aminooxyacetic Acid; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D001833:Body Temperature Regulation / Q000502:physiology; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D005334:Fever / Q000139:chemically induced; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007031:Hypothalamus / Q000378:metabolism; D007035:Hypothermia / Q000503:physiopathology; D000860:Hypoxia; D008070:Lipopolysaccharides; D008297:Male; D008845:Microinjections; D011301:Preoptic Area / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000503:physiopathology*
chemical_list: D008070:Lipopolysaccharides; D000625:Aminooxyacetic Acid; D003541:Cystathionine beta-Synthase; D006862:Hydrogen Sulfide
keywords: Fever; Hypothalamus; Hypothermia; LPS; PGD(2); Systemic inflammation