Stereoselective actions of hepoxilins A3 and B3 and their cyclopropane analogs (HxdeltaA3 and HxdeltaB3) on bradykinin and PAF-evoked potentiation of vascular leakage in rat skin.
Native hepoxilins (Hx) A3 and B3 as well as their synthetic cyclopropane analogs, HxdeltaA3 and HxdeltaB3 are inactive on their own in causing changes in vascular permeability in rat skin measured by leakage of plasma-bound Evans Blue dye. Several of these compounds, however, were observed to potentiate the leakage of dye evoked by bradykinin (BK) and platelet-activating factor (PAF). The syn epimer of HxA3 was effective in potentiating dye leakage evoked by BK but not by PAF. The syn epimer of HxB3, on the other hand, was capable of potentiating both BK- and PAF-evoked plasma protein leakage. The anti epimer of both hepoxilins was inactive. In contrast, the anti epimer of the cyclopropane analog HxdeltaA3 potentiated only the BK-evoked changes, whereas the anti epimer of HxdeltaB3 potentiated only the PAF-evoked changes in dye leakage. The corresponding other epimer of each compound was inactive. Our findings indicate that the hepoxilin cyclopropane analogs appear to mimic the actions of the native compounds.
Wang
M M
MM
Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
Demin
P M
PM
Pace-Asciak
C R
CR
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000279:Administration, Cutaneous; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects*; D003521:Cyclopropanes / Q000494:pharmacology*; D004357:Drug Synergism; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000098:blood supply / Q000187:drug effects*; D013237:Stereoisomerism
D003521:Cyclopropanes; D010972:Platelet Activating Factor; C061163:11-glutathionylhepoxilin A3; C022948:10-hydroxy-11,12-epoxyeicosa-5,8,14-trienoic acid; D015126:8,11,14-Eicosatrienoic Acid; D001920:Bradykinin