Basal release of endothelin-1 and the influence of the ETB receptor on single vessel hydraulic permeability.

BACKGROUND

Endothelin-1 (ET-1) has a direct permeability decreasing effect on the microvasculature. The present study was designed to test the hypothesis that this effect is mediated via the endothelin B (ETB) receptor located on the microvascular endothelium and to determine whether basal microvascular permeability is dependent on constitutive release of ET-1. To isolate the direct effect of ET-1, experiments were conducted under conditions in which hydraulic and oncotic pressures were controlled.

METHODS

Postcapillary venules in the rat mesentery were perfused in situ, and paired measurements of hydraulic permeability (Lp) were obtained using the modified Landis micro-occlusion method. Lp measured after a 15-minute perfusion with the ETB receptor blocker BQ-788 (1 micromol/L) was compared with measures of Lp obtained after perfusion with a combined mixture of BQ-788 and ET-1 (80 pmol/L) (n = 6). In addition, the effect of basal endogenous ET-1 was tested by measuring the effects of BQ-788 perfusion on Lp (n = 6).

RESULTS

Units for Lp are mean +/- SE x 10(-8) cm x s(-1) cm H2O(-1). ETB receptor blockade prevented any decrease in Lp induced by ET-1 (BQ-788 alone = 7.9 +/- 0.7; BQ-788 + ET-1 = 8.2 +/- 0.8;p = 0.5). Under basal conditions and in the absence of exogenous ET-1, ETB receptor blockade led to a significant increase in Lp from 6.8 +/- 0.9 to 9.7 +/- 1.2 (p = 0.001).

CONCLUSION

Decreases in microvascular permeability in single postcapillary venules after the administration of ET-1 are mediated via the ETB receptor. Constitutive release of ET-1 from the microvascular endothelium also plays a role in maintaining basal levels of permeability. These findings suggest important roles for ET-1 in maintaining and modulating microvascular permeability.