Endothelin-1 decreases postcapillary fluid efflux via prostacyclin release.
BACKGROUND
Endothelin-1 (ET-1) decreases water efflux across the endothelial barrier (Lp). ET-1 may exert this permeability-decreasing effect by stimulating prostacyclin (PGI2) release. The purposes of this study were to (1) examine the effect of PGI2 on Lp, (2) measure Lp after inhibition of PGI(2) synthesis, and (3) determine the effect of ET-1 on Lp during inhibition of PGI2 production.


METHODS
After microscopic cannulation of mesenteric venules, Lp was measured during PGI2 infusion (0.1 micromol/L, 1 micromol/L, and 10 micromol/L; n = 6 in each group). Lp was also measured after 100 micromol/L of the PGI2 synthase inhibitor, tranylcypromine (TCPN) (n = 6). Finally, the influence of ET-1 on Lp during PGI2 synthase inhibition was assessed (n = 6).


RESULTS
Compared to baseline Lp of 1.05 +/- 0.06, PGI2 decreased Lp at 1 micromol/L (Lp = 0.63 +/- 0.03, P < .003) and 10 micromol/L (Lp = 0.52 +/- 0.04, P < .0001). TCPN increased Lp compared to baseline (P < .0001). Compared to ET-1 alone, venules perfused with TCPN + ET-1 increased Lp (P < .005). Units for Lp ) are 10(-7) cm x sec(-1) x cmH2O(-1).


CONCLUSIONS
We found that (1) PGI2 decreases Lp, (2) inhibition of PGI2 synthesis increases Lp, and (3) permeability-decreasing effects of ET-1 can be blocked by inhibiting PGI2 synthesis. These data suggest that constitutive production of PGI2 modulates basal microvessel permeability and that ET-1 may exert its permeability-decreasing effect via the stimulation of PGI2 release.
Department of Surgery, University of California San Francisco-East Bay, Alameda County Medical Center, Oakland, CA 94602, USA.
Gregory P
GP
Victorino
Terry J
TJ
Chong
Brian
B
Curran
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D011464:Epoprostenol / Q000096:biosynthesis* / Q000494:pharmacology; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley
D019332:Endothelin-1; D011464:Epoprostenol