Endothelin 1 and prostacyclin attenuate increases in hydraulic permeability caused by platelet-activating factor in rats.
We have previously documented that endothelin 1 (ET-1) and prostacyclin (PGI2) decrease basal state hydraulic permeability (Lp). The aim of this study was to investigate the ability of ET-1 and PGI2 to modulate transendothelial fluid flux during situations in which Lp was artificially elevated with platelet-activating factor (PAF). We hypothesized that ET-1 and PGI2 administration before PAF exposure would prevent the increase in Lp secondary to PAF. In addition, in a potentially more clinically relevant situation, we also hypothesized that ET-1 and PGI2 administration after PAF exposure would attenuate the increase in Lp secondary to PAF. Microvascular Lp was measured in rat mesenteric postcapillary venules. Exposure to 10 nM PAF increased Lp 4-fold (P < 0.001). If the administration of 80 pM ET-1 or 10 microM PGI2 was completed before PAF exposure, no PAF-associated increase in Lp was observed (P < 0.001). The administration of ET-1 or PGI2 after PAF exposure attenuated the peak increase in Lp caused by PAF alone by 55% and 57%, respectively (P < 0.001). We conclude that ET-1 and PGI2 administration before PAF exposure prevents PAF-induced elevations in Lp, and in a more clinically relevant situation, ET-1 and PGI2 administered after PAF exposure attenuate the PAF-induced increase in Lp. Endothelin 1 and PGI2 receptors may provide important therapeutic targets for decreasing the microvascular fluid leak-associated morbidity resulting from shock and sepsis.
Cureton
Elizabeth L
EL
University of California, San Francisco-East Bay, Department of Surgery, Oakland, California, USA.
Chong
Terry J
TJ
Kwan
Rita O
RO
Dozier
Kristopher C
KC
Sadjadi
Javid
J
Curran
Brian
B
Victorino
Gregory P
GP
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D006224:Cricetinae; D019332:Endothelin-1 / Q000494:pharmacology*; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D008647:Mesocricetus; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014699:Venules / Q000187:drug effects
D019332:Endothelin-1; D010972:Platelet Activating Factor; D011464:Epoprostenol