Sphingosine-1-phosphate and the "albumin effect" on rat venular microvessels

Sphingosine‐1‐phosphate (S1P) is carried in plasma bound to albumin (40%) and high density lipoprotein (60%). Because constant S1P is required to maintain a stable baseline endothelial barrier in individually perfused microvessels (Am J Physiol 303: H825, 2012), we tested the hypothesis that removal of albumin from a perfusate in rat venular microvessels would decrease available S1P and increase permeability. We measured the apparent solute permeability coefficient (P s ) of the vessel wall to fluorescently labeled albumin. Unlike the Landis‐Michel method to measure hydraulic conductivity, P s measurement does not require the use of RBCs, a principal source of S1P, as flow markers. Perfusates used to measure P s were initially conditioned by 20 min exposure to rat RBCs to provide a baseline level of S1P. Control perfusate was Ringer with fatty acid free albumin (10 mg/ml); test was Ringer alone. The control solution had a stable S1P concentration (0.34 ± 0.03 μM) close to normal plasma value and established a stable baseline P s of 0.8 ± 0.2 × 10 −6 cm/sec. The test solution with no albumin contained only 0.03 ± 0.01 μM S1P and increased permeability more than 10‐fold (n=4). We conclude that part of the well‐known “albumin effect” depends on the transport of S1P by albumin from RBCs to the endothelium. NIH HL28607.