Gender Differentiation And Mechanism Of Endothelial Nitric Oxide Synthase In Different Tissues In Response To Inflammatory Stimuli

Objective: To investigate the gender differences of endothelial nitric oxide synthase(eNOS)in different tissues in response to inflammatory stimuli and elucidate its mechanism.Methods: Rat sepsis was induced by intraperitoneal injection of lipopolysaccharide(LPS,10 mg/kg),24 hours after LPS injection,the levels of eNOS mRNA and protein were measured by qPCR or Western blot,respectively.Estrogen plasma levels were measured using ELISA.Performing chromatin immunoprecipitation(ChIP)to detect the activity of eNOS promoter.Endothelial-dependent vasorelaxation to acetylcholine in mesenteric arteries and aorta isolated from male and female rats were also been measured.Results: Female rats treated with LPS demonstrated either increased levels of eNOS protein or mRNA expression in mesenteric arteries,compared with control subjects(P<0.05),but not in aorta.While in LPS treated male rats,both eNOS protein and mRNA levels in mesentericarteries or aorta were decreased,compared with those of control male rats(P<0.05).ChIP assays showed that LPS treatment might markedly increase the binding of Sp1 to its DNA elements in eNOS promoters in female rats,but diminish the equal binding in male rats.LPS significantly increased the relaxation response induced by ACh in mesenteric arteries,while significantly decreased in the thoracic aorta in female rats.And the expressions of eNOS were increased in mesenteric arteries from LPS-injected female rats,this action may been reversed by fulvesrtant treatment.Conclusion: LPS might increase levels of eNOS protein in mesenteric arteries of female rats,and this may caused by estrogen up-regulate eNOS promoter activity.Estrogen participates in mediating gender differences in eNOS response to sepsis in mesenteric artery...