Central NO-cGMP pathway in thermoregulation and survival rate during polymicrobial sepsis.
Sepsis induces production of inflammatory mediators such as nitric oxide (NO) and causes physiological alterations, including changes in body temperature (Tb). We evaluated the involvement of the central NO-cGMP pathway in thermoregulation during sepsis induced by cecal ligation and puncture (CLP), and analyzed its effect on survival rate. Male Wistar rats with a Tb probe inserted in their abdomen were intracerebroventricularly injected with 1 microL NG-nitro-L-arginine methyl ester (L-NAME, 250 microg), a nonselective NO synthase (NOS) inhibitor; or aminoguanidine (250 microg), an inducible NOS inhibitor; or 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 0.25 microg), a guanylate cyclase inhibitor. Thirty minutes after injection, sepsis was induced by cecal ligation and puncture (CLP), or the rats were sham operated. The animals were divided into 2 groups for determination of Tb for 24 h and assessment of survival during 3 days. The drop in Tb seen in the CLP group was attenuated by pretreatment with the NOS inhibitors (p < 0.05) and blocked with ODQ. CLP rats pretreated with either of the inhibitors showed higher survival rates than vehicle injected groups (p < 0.05), and were even higher in the ODQ pretreated group. Our results showed that the effect of NOS inhibition on the hypothermic response to CLP is consistent with the role of nitrergic pathways in thermoregulation.
Biociências Aplicadas à Farmácia, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo 14040-904, Brasil.
G R
GR
Oliveira-Pelegrin
L G S
LG
Branco
M J A
MJ
Rocha
D000818:Animals; D001831:Body Temperature / Q000502:physiology; D001833:Body Temperature Regulation / Q000502:physiology*; D002432:Cecum; D006152:Cyclic GMP / Q000502:physiology*; D006146:Guanidines / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D008026:Ligation; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D011677:Punctures; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000201:enzymology / Q000382:microbiology / Q000401:mortality* / Q000503:physiopathology*; D015996:Survival Rate / Q000639:trends
D006146:Guanidines; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; C004479:pimagedine