Protective effect of estradiol on acute lung inflammation induced by an intestinal ischemic insult is dependent on nitric oxide

• Grant number: 14/50143-5
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: April 01, 2014
• End date: September 30, 2014
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Wothan Tavares de Lima
• Grantee: Wothan Tavares de Lima
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Sexual dimorphism modulates the profile of Th1 and Th2 lymphocytes, and accordingly sex hormones may modulate ALI by intestinal I/R. Studies indicate that gut of female is more resistant than the male to deleterious effects of ischemic injury. Here we investigated the effect of estradiol on the lung inflammation after intestinal I/R and its interaction with the NO pathway. Anesthetized rats submitted to 7 days ovariectomy (OVx) were subjected to occlusion of the superior mesenteric artery (SMA) during 45 min, followed by 2 h of reperfusion. Rats were treated with E2 (17{3-estradiol, 280pg/kg, s.c.) 24 h before I/R and/or with the NO synthase inhibitor L-NAME (5 mg/kg, i. v.). Lung vascular permeability (LVP); neutrophil recruitment to the tissues (MPO) and endothelial NO synthase (eNOS) protein were assessed. In OVx rats, LVP and MPO were increased after intestinal l/R as compared to intact controls. E2 reverted the LVP, but not MPO. The E2 protective effect on LVP was abolished by L- NAME; moreover, an increase of L VP even when compared to OVx-rats treated only with L-NAME was observed. Lung eNOS expression was reduced in OVx-I/R rats in comparison to intact controls and the E2 inhibited this effect. E2 is able to reduce lung inflammation due to intestinal ischemia/reperfusion, but with the concomitant blockade of NOS activity, this effect is abolished. E2 reduces lung inflammation after intestinal ischemia/reperfusion and exerts these effects by modulating eNOS protein expression in the lungs. (AU)