Microvascular permeability in the absence of Epac1 activity

Abstract

Epac1 is a cAMP binding protein which through intrinsic guanine nucleotide exchange factor activity couples cAMP production to activation of Rap. Epac1 is abundant in blood vessel endothelium, and may contribute in the cAMP mediated attenuation of inflammatory leakage by stabilizing the endothelial barrier. To establish how basal vascular permeability is affected in the absence of Epac1 in vivo we measured blood‐to‐tissue albumin clearance and plasma volumes with a dual‐label isotope technique in isofluorane anesthetized Epac1 knockout (KO) and wt mice. Albumin permeability, calculated as the ratio of albumin clearance to local vascular volume, was significantly increased in back skin, quadriceps muscle, inguinal fat and brown fat of Epac1 KO compared to wt mice. Furthermore, there was a significant increase in water content in inguinal fat of Epac1 KO mice and with a similar tendency observed in back skin. We conclude that intact signaling through Epac1 may be of importance to maintain the basal endothelial barrier integrity in vivo and thus prevent excessive protein leakage into the interstitium of skin, muscle and fat under steady‐state conditions.The work was supported by The Research Council of Norway and The Western Norway Health Authority. The following have contributed to produce and characterize the Epac1 KO mouse: C. Krakstad, K. Kristiansen, and L. Madsen.