title: Protective effect of estradiol on acute lung inflammation induced by an intestinal ischemic insult is dependent on nitric oxide.
abstract: BACKGROUND
  It has been shown that the innate immune system mediates acute lung inflammation triggered by intestinal trauma. Sexual dimorphism modulates the profile of TH1 and TH2 lymphocytes, and accordingly sex hormones may modulate acute lung inflammation by intestinal ischemia/reperfusion (I/R). Studies indicate that female rats are relatively resistant to organ injury caused by hemorrhagic shock and that the gut of female is more resistant than that of the male to deleterious effects of ischemic injury. At the present study, we investigated the effect of estradiol (E(2)) on the lung inflammation after intestinal I/R and its interaction with the nitric oxide (NO) pathway.
  
  
  METHODS
  Anesthetized female rats submitted or not to 7 days ovariectomy (OVx) were subjected to occlusion of the superior mesenteric artery during 45 min, followed by 2 h of reperfusion. Groups of rats were treated with E(2) (17β-estradiol, 280 μg/kg, s.c.) 24 h before ischemia and/or with the nonselective NO synthase inhibitor L-NAME (Nω-nitro-L-arginine methyl ester hydrochloride) (5 mg/kg, i.v.). In a parallel set of experiments, the selective NO synthase inhibitor, aminoguanidine (50 mg/kg i.v.), was given 1 h before ischemia. In all groups, lung vascular permeability (LVP) was assessed using the Evans blue dye extravasation method, neutrophil recruitment to the tissues by the standard myeloperoxidase (MPO) method, and endothelial NO synthase (eNOS) protein expression by Western blot.
  
  
  RESULTS
  In OVx rats, LVP and MPO were increased after intestinal I/R as compared with intact controls. Estradiol reverted the LVP, but not MPO. Aminoguanidine reduced LVP in OVx rats. The E(2) protective effect on LVP was abolished by L-NAME; moreover, an increase in LVP even when compared with OVx rats treated only with L-NAME was observed. In addition, lung eNOS protein expression was reduced in OVx-I/R rats in comparison to intact controls and the E(2) inhibited this effect.
  
  
  CONCLUSIONS
  Estradiol treatment is able to reduce lung inflammation due to intestinal I/R, but with the concomitant blockade of NOS activity, this effect is abolished. Nitric oxide probably reduces the vascular deleterious effects of intestinal I/R, and E(2) pretreatment reduces lung inflammation after intestinal I/R and exerts these effects by modulating eNOS protein expression in the lungs.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Breithaupt-Faloppa
authors.affiliation: Laboratory of Cardiovascular Surgery and Physiopathology of Circulation (LIM-11), Heart Institute (InCor), Medicine School, São Paulo, Brazil.
authors.forename: A C
authors.initials: AC
authors.lastname: Breithaupt-Faloppa
authors.forename: Evelyn Thais
authors.initials: ET
authors.lastname: Fantozzi
authors.forename: E T
authors.initials: ET
authors.lastname: Fantozzi
authors.forename: Mayara Munhoz
authors.initials: MM
authors.lastname: de Assis Ramos
authors.forename: M M
authors.initials: MM
authors.lastname: Assis-Ramos
authors.forename: Luana Beatriz
authors.initials: LB
authors.lastname: Vitoretti
authors.forename: L B
authors.initials: LB
authors.lastname: Vitoretti
authors.forename: Gisele Kruger
authors.initials: GK
authors.lastname: Couto
authors.forename: G K
authors.initials: GK
authors.lastname: Couto
authors.forename: Adriana
authors.initials: A
authors.lastname: Lino-dos-Santos-Franco
authors.forename: Luciana Venturini
authors.initials: LV
authors.lastname: Rossoni
authors.forename: L V
authors.initials: LV
authors.lastname: Rossoni
authors.forename: Ricardo Martins
authors.initials: RM
authors.lastname: Oliveira-Filho
authors.forename: R M
authors.initials: RM
authors.lastname: Oliveira-Filho
authors.forename: Bernardo Boris
authors.initials: BB
authors.lastname: Vargaftig
authors.forename: B B
authors.initials: BB
authors.lastname: Vargaftig
authors.forename: Wothan
authors.initials: W
authors.lastname: Tavares-de-Lima
authors.forename: W
authors.initials: W
authors.lastname: Tavares-de-Lima
mesh_terms: D000818:Animals; D004958:Estradiol / Q000627:therapeutic use*; D005260:Female; D007422:Intestines / Q000098:blood supply*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011014:Pneumonia / Q000188:drug therapy* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009569:Nitric Oxide; D004958:Estradiol