Role of endothelin-1 and cyclic nucleotides in ischemia/reperfusion-mediated microvascular leak

The Journal of Trauma
René RamirezG P Victorino

Abstract

A consequence of ischemia/reperfusion (IR) is endothelial barrier dysfunction and intravascular volume loss. The purposes of our study are to explore the impact of: 1) cyclic guanosine monophosphate (cGMP) synthesis inhibition, 2) cyclic adenosine monophosphate (cAMP) synthesis inhibition, 3) treatment with endothelin-1, and 4) endothelin-1 (ET-1)-mediated cAMP changes on IR-induced fluid leak. We hypothesize that IR-mediated microvascular fluid leak results from increased cGMP activity and ET-1 decreases IR-induced fluid leak via cAMP. A micro-cannulation technique was used to determine fluid leak or hydraulic permeability (Lp) in rat mesenteric venules. Lp was measured during IR and after treatment with 1) cGMP synthesis inhibitor (LY83583,10 micromol/L) 2) cAMP synthesis inhibitor (2',5'dideoxyadenosine,10 micromol/L), 3) ET-1 (80 pM), and 4) cAMP synthesis inhibitor plus ET-1 (n=6 in each group; Lp represented as mean+/-standard error of the mean; units 10-cm/sec/cmH2O). IR resulted in an increase in Lp (Lp=7.07+/-0.20) sevenfold above baseline (1.05+/-0.31) (p<or=0.001). Compared with IR alone, 1) pretreatment with cGMP synthesis inhibitor completely blocked IR-induced fluid leak (Lp=1.08+/-0.18) (p<or=0.001), 2) pretreatm...Continue Reading

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Citations

Dec 25, 2010·Journal of Applied Physiology·Elizabeth L CuretonGregory P Victorino
Apr 14, 2007·International Journal of Urology : Official Journal of the Japanese Urological Association·Chabouk AnasSeiichi Matsuo
Dec 2, 2017·The Journal of Trauma and Acute Care Surgery·Peter J BruhnHasan B Alam

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