Local vasodilator effect of platelet activating factor in the gastric, mesenteric and femoral arteries of the dog.
Platelet activating factor (PAF) has been postulated to have vascular effects that contribute to gastrointestinal ulceration and necrosis produced during endotoxin shock. To evaluate the regional arterial effects of PAF and its interaction with cyclooxygenase metabolites of arachidonic acid, we infused increasing doses of PAF (calculated to achieve an initial plasma concentration of 2 X 10(-9), 10(-8), 5 X 10(-8) M) into the gastric, mesenteric and femoral arteries in the presence or absence of indomethacin (5 mg/kg) in anesthetized dogs. During a 5-min infusion of PAF, regional resistances in the gastric, mesenteric and femoral arterial circulations decreased transiently and dose dependently in the initial phase (minute 1 and 2) by 71, 65 and 64%, respectively. In the late phase (minute 3-5), the arterial resistance returned gradually toward base line in the gastric and mesenteric circulations but remained reduced in the femoral arterial circulation. In the vehicle-treated group, the effect of PAF was reproducible. In the indomethacin-treated group, the initial vasodilator response to PAF was not altered in any of the arterial circulations, but in the late phase, the return of arterial resistance toward base line in the gastric and mesenteric circulations was attenuated by indomethacin (P less than .05). In contrast, in the femoral circulation, indomethacin enhanced the return of the arterial resistance (P less than .05) toward base line.(ABSTRACT TRUNCATED AT 250 WORDS)
Chu
K M
KM
Division of Clinical Pharmacology C-237, University of Colorado Health Sciences Center, Denver.
Gerber
J G
JG
Nies
A S
AS
D000818:Animals; D004285:Dogs; D005263:Femoral Artery / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D007536:Isomerism; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D013270:Stomach / Q000098:blood supply; D014664:Vasodilation / Q000187:drug effects*
D010972:Platelet Activating Factor; D007213:Indomethacin