Platelet-activating factor contributes to postischemic vasospasm.
BACKGROUND
The purpose of the present study was to determine if platelet-activating factor is an important mediator that produces vasospasm during reperfusion after ischemia in skeletal muscle.


METHODS
A vascular isolated cremaster muscle in male Sprague-Dawley rats was coupled with local intraarterial drug infusion as a model to study microcirculation responses to ischemia/reperfusion injury. Arteriole diameters and capillary perfusion were measured using intravital microscopy. Group 1: platelet-activating factor dose response. Group 2: Effects of a cyclooxygenase inhibitor; indomethacin, and a thromboxane synthetase inhibitor, imidazole, on the response to platelet-activating factor. Group 3: Effects of nitric oxide synthesis inhibitor; N(omega)-nitro-L-arginine methyl ester, on the response to platelet-activating factor. Group 4: Effects of a platelet-activating factor receptor antagonist, CV-3988, indomethacin, and imidazole after 4 h of warm ischemia and reperfusion.


RESULTS
Intraarterial infusion of platelet-activating factor produced a dose-related but mild vasoconstriction. Pretreatment with indomethacin or imidazole resulted in significant vasodilation actually emanating from platelet-activating factor infusion. Nitric oxide inhibition (with N(omega)-nitro-L-arginine methyl ester) enhanced the vasoconstriction produced by platelet-activating factor. Pretreatment with CV-3988, indomethacin, or imidazole significantly attenuated ischemia/reperfusion-induced vasospasm and capillary no-reflow in the cremaster muscles.


CONCLUSIONS
Ischemia/reperfusion-induced vasoconstriction is at least in part mediated by platelet-activating factor and thromboxane A(2).
Wang
W Z
WZ
Center for Applied Microcirculatory Research, University of Louisville, Louisville, Kentucky 40292, USA. wzwang01@gwise.louisville.edu
Guo
S Z
SZ
Tsai
T M
TM
Anderson
G L
GL
Miller
F N
FN
D000818:Animals; D005837:Genitalia, Male; D007269:Injections, Intra-Arterial; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D018482:Muscle, Skeletal / Q000098:blood supply*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects
D010972:Platelet Activating Factor; D009569:Nitric Oxide; D013928:Thromboxane A2