Sphingosine‐1‐phosphate and the “albumin effect” on rat venular microvessels

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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 (Ps) of the vessel wall to fluorescently labeled albumin. Unlike the Landis‐Michel method to measure hydraulic conductivity, Ps measurement does not require the use of RBCs, a principal source of S1P, as flow markers. Perfusates used to measure Ps 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 Ps 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.