The Cardiovascular Effects Of Irisin In Rostral Ventrolateral Medulla Of Septic Rats

Irisin,a newly defined muscle factor,has been proved been involved into the pathogenesis in inflammatory diseases.As the key area of sympathetic activity,the implication of the rostral ventrolateral medulla(RVLM)in hypotensive shock in sepsis has been extensively reported.However,whether irisin is involved into the pathophysiology of sepsis through the RVLM mechanism has not been well determined.OBJECTIVETo study the cardiovascular effects of irisin within the RVLM and explore their signaling pathway in sepsis rats.Methods1.Male SD rats were divided into control group,sham operation group and sepsis group.The expression of irisin in the RVLM was detected by immunohistochemistry.2.Artificial cerebrospinal fluid(aCSF)or different doses of irisin was unilateral microinjection into the RVLM.The responses of blood pressure(BP)or heart rate(HR)to intra-RVLM was observed.3.ACSF,l-type calcium channel blockers,non-selective glutamate receptor antagonists,non-selective nitric oxide synthase inhibitors or potassium channel blockers were prior applied into the RVLM of rats to explore the mechnisms of the intra-RVLM cardiovascular effects of irisin.Results1.The expression of irisin the RVLM of rats in the sepsis group was significantly decreased compared with the normal control group(P<0.05).2.Unilateral microinjection of irisin into the RVLM significantly incrceased BP and HR of septic rats(P<0.05).3.Importantly,prior application of nicardipine,n-nitro-l-arginine methyl methyl or glyphenuride partly decreased the cardiovascular effect of intra-RVLM irisin(P < 0.05).However,prior applicaion of canine uroquinic acid didn't alter the cardiovascular effects of intr-RVLM irisin(P > 0.05).Conclusion1.Irisin is probably involved in the pathological process of sepsis by low expression in the RVLM.2.In the RVLM of sepsis rats,irisin produces hypertension and heart rate in sepsis rats through the NO pathway,L-type calcium channel,or KATP channel signaling pathway.The decrease of cardiovascular effects caused by low expression of irisin within the RVLM might be involved into the pathological processes related to sepsis.