Interaction of Endothelin-1 and Nitric Oxide in Endothelial Barrier Failure in the Cat Hindlimb

Objective:To determine the interactions of endothelin-1 (ET-1) and nitric oxide (NO) in the regulation of endothelial barrier function in skeletal muscle. Methods:The protein sieving coefficient (1 − σf) was measured as an index of microvascular permeability in the isolated, perfused cat hindlimb preparation. The measurement was made to determine 1) the effects of ET-1 and NO on basal permeability by blocking the ETAreceptor with BQ123 and NO production with the NO-synthase inhibitors L-NAME or L-NMMA; 2) if elevated NO (SNAP) affects permeability; and 3) the interaction of ET-1 and NO by ascertaining if NO-synthase inhibition or elevated NO can block the ET-1-induced permeability increases. Additionally, vascular resistance was determined under these conditions to see if increased microvascular pressures or increased shear stress might play a role in the permeability changes. Results:Blocking either the ETAreceptor or basal NO production did not affect basal permeability. Likewise, raising NO levels did ...