Direct actions of endothelin-1 on single vessel hydraulic permeability

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 (Lp) when microvascular hydraulic and oncotic pressures are controlled.

Postcapillary venules in the rat mesentery were perfused in situ and paired measurements of Lp obtained by using the modified Landis micro-occlusion method. Lp measured after a 15-minute perfusion with Ringer's albumin solution (control) was compared with Lp 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).

Baseline L for all vessels averaged (+/- SE) 8.1 +/-0.8 x 10(-8) cm x sec(-10 x cm H2O(-1) and was not significantly different between groups. Perfusion with either control or 8 pM ET-1 did not significantly change the Lp of any of the vessels. Significant decreases in Lp of 40 to 60% were observed in venules perfused with 80 pM ET-1. The average Lp 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 Lp to baseline values.

Low-dose ET-1 did not directly increase Lp in postcapillary venules. ET-1 at 80 pM, however, significantly decreased Lp. 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.