Direct actions of endothelin-1 on single vessel hydraulic permeability

Background: There is evidence that endothelin-1 (ET-1) increases extravasation of fluid and protein into vascular beds. The present study was designed to determine the direct effects of ET-1 on hydraulic permeability (L(p)) when microvascular hydraulic and oncotic pressures are controlled. Methods: Postcapillary venules in the rat mesentery were perfused in situ and paired measurements of L(p) obtained by using the modified Landis micro-occlusion method. L(p) measured after a 15-minute perfusion with Ringer's albumin solution (control) was compared with L(p) after a subsequent 15-minute perfusion with one of three treatments: control (n = 4), 8 pM ET-1 (n = 6), or 80 pM ET-1 (n = 6). Results: Baseline L(p) for all vessels averaged (± SE) 8.1 ± 0.8 x 10^-8 cm · sec^-1 · cm H₂O^-1 and was not significantly different between groups. Perfusion with either control or 8 pM ET-1 did not significantly change the L(p) of any of the vessels. Significant decreases in L(p) of 40 to 60% were observed in venules perfused with 80 pM ET-1. The average L(p) in this group was 9.9 ± 1.4 during baseline and decreased to 5.0 ± 0.7 during ET-1 perfusion (p = 0.003). Washout of 80 pM ET-1 for periods of up to 15 minutes did not return L(p) to baseline values. Conclusion: Low-dose ET-1 did not directly increase Lp in postcapillary venules. ET-1 at 80 pM, however, significantly decreased L(p). These data implicate factors other than a direct permeability-increasing effect in ET-1. At higher concentrations, ET-1 may have a protective effect on endothelial barrier function.