Endothelin-1 decreases postcapillary fluid efflux via prostacyclin release

Background. Endothelin-1 (ET-1) decreases water efflux across the endothelial barrier (L-p). ET-1 may exert this permeability-decreasing effect by stimulating prostacyclin (PGI(2)) release. The purposes of this study were to (1) examine the effect of PGI(2) on L-p, (2) measure L-p after inhibition of PGI(2) synthesis, and (3) determine the effect of ET-1 on L-p during inhibition of PGI(2) production. Methods. After microscopic cannulation of mesenteric venules, L-p was measured during PGI(2) infusion (0.1 mumol/L, 1 mumol/L, and 10 mumol/L; n = 6 in each group). L-p was also measured after 100 mumol/L of the PGI(2) synthase inhibitor, tranylcypromine (TCPN) (n = 6). Finally, the influence of ET-1 on L-p during PGI(2) synthase inhibition was assessed (n = 6). Results. Compared to baseline L-p of 1.05 +/- 0.06, PGI(2) decreased L-p at 1mumol/L (L-p = 0. 63 0.03, P < .003) and 10 mumol/L (L-p = 0.52 +/- 0.04, P < .0001). TCPN increased L-p compared to baseline (P < .0001). Compared to ET-1 alone, venules perfused with TCPN + ET-1 increased L-p (P < .005). Units for L-p are 10(-7) cm(.)sec(-1.)cmH(2)O(-1). Conclusions. We found that (1) PGI(2) decreases L-p, (2) inhibition of PGI(2) synthesis increases L-p, and (3) permeability-decreasing effects of ET-1 can be blocked by inhibiting PGI(2) synthesis. These data suggest that constitutive production of PGI(2) modulates basal microvessel permeability and that ET-1 may exert its permeability-decreasing effect via the stimulation of PGI(2) release.