Platelet-activating factor increases vascular resistance in rat hindquarters by thromboxane A2.
The effects of platelet-activating factor (PAF) on vascular resistance and capillary permeability were studied in the isolated rat hindquarter. Six groups were studied (n = 30): control; PAF alone (1.4 microM); and PAF (1.4 microM) pretreated with ibuprofen (30 mg/kg), thromboxane A2 (TxA2)-receptor antagonist (BM-13505, 2 mg/kg), PAF-receptor antagonist (WEB-2086, 5 mg/kg), or dexamethasone (5 mg/kg). The vascular resistance was calculated, and the reflection coefficient (sigma) was determined as an index of capillary permeability. Exogenous PAF caused a threefold increase in vascular resistance peaking at 5 min and a 2.5-fold increase in capillary permeability. The increased vascular resistance caused by PAF alone was significantly attenuated by ibuprofen, BM-13505, and dexamethasone. The PAF-induced permeability was neither attenuated by ibuprofen nor BM-13505. However, both the increased vascular resistance and permeability were blocked and attenuated by WEB-2086 and dexamethasone, respectively. We conclude that TxA2 mediates the PAF-induced increased vascular resistance; however, the increased vascular permeability is independent of the formation of TxA2 in the isolated hindquarter.
Rizzo
A
A
Department of Surgery, College of Medicine, University of South Alabama, Mobile 36688, USA.
Taylor
A E
AE
Townsley
M I
MI
Logsdon
P
P
Khimenko
P L
PL
Fletcher
J R
JR
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply; D007052:Ibuprofen / Q000494:pharmacology; D008297:Male; D010648:Phenylacetates / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D013928:Thromboxane A2 / Q000502:physiology*; D013931:Thromboxanes / Q000037:antagonists & inhibitors; D014230:Triazoles / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects*
D001381:Azepines; D010648:Phenylacetates; D010972:Platelet Activating Factor; D013449:Sulfonamides; D013931:Thromboxanes; D014230:Triazoles; C052518:WEB 2086; D013928:Thromboxane A2; C051762:daltroban; D007052:Ibuprofen