G P Victorino1, D H Wisner, V L Tucker. 1. Department of Surgery, University of California, Davis, Medical Center, Sacramento 95817-2214, USA.
Abstract
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 (Lp) when microvascular hydraulic and oncotic pressures are controlled. METHODS: 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). RESULTS: 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. CONCLUSION: 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.
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 (Lp) when microvascular hydraulic and oncotic pressures are controlled. METHODS: 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). RESULTS: 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. CONCLUSION: 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.
Authors: Elizabeth L Cureton; Aaron Strumwasser; Rita O Kwan; Kristopher C Dozier; Brian Curran; Javid Sadjadi; Gregory P Victorino Journal: J Appl Physiol (1985) Date: 2010-12-23
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