Vasoconstrictor effects of platelet-activating factor in the hamster cheek pouch microcirculation: dose-related relations and pathways of action.
Platelet-activating factor (PAF) has been implicated as a potential mediator of inflammatory processes. In this study, we quantified the effects of PAF on vessel diameter in a microvascular bed and investigated the biochemical pathways of this compound. The hamster cheek pouch microcirculation was observed with intravital microscopy. Experiments were video-recorded and analyzed with an image shearing device. Vasoconstriction was the predominant vasomotor response to PAF. PAF (10(-10) -10(-5) M) was applied topically to the pouch for 3 minutes. Arterioles ranging in size from 8 to 15 micron were the most sensitive, and they constricted completely in response to PAF 10(-7) and 10(-5) M. Arterioles 21-40 micron in diameter constricted to 12-17% of control after PAF at 10(-7) and 10(-5) M, respectively; they reopened to about 70% of their control value after a few minutes and remained near that size throughout the experiment. Arterioles 41-60 micron in diameter constricted to about 20% control size in response to 10(-7) and 10(-5) M PAF, and by the end of the experiment, these vessels had returned to about 90% control size. To determine the pathways of PAF actions, inhibitors of the arachidonic acid cascade and receptor blockers were used. Dexamethasone, indomethacin, OKY-046 (a thromboxane A2 synthetase inhibitor), and kadsurenone (a PAF-receptor blocker) blocked the vasoconstrictor response to PAF. Our experiments demonstrate that PAF-produced arteriolar constriction in a microvascular bed is 1) dose-related, 2) dependent upon vessel size, 3) largely due to thromboxane A2 activity, and 4) mediated by PAF-receptor interactions.
Dillon
P K
PK
Department of Physiology, UMDNJ-New Jersey Medical School, Newark 07103-2757.
Ritter
A B
AB
Durán
W N
WN
D000818:Animals; D001160:Arterioles / Q000033:anatomy & histology / Q000187:drug effects; D001572:Benzofurans / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002610:Cheek / Q000098:blood supply*; D006224:Cricetinae; D016861:Cyclooxygenase Inhibitors; D004305:Dose-Response Relationship, Drug; D006400:Hematocrit; D017705:Lignans; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D013928:Thromboxane A2 / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects
D001572:Benzofurans; D016861:Cyclooxygenase Inhibitors; D017705:Lignans; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D013928:Thromboxane A2; C044540:kadsurenone