Influence of platelet-activating factor on cerebral microcirculation in rats part 1. Systemic application

Background and Purpose-Platelet-activating factor (PAF) has been demonstrat ed to have a mediator function in shock, with some of its deleterious effec ts being attributed to its influence on microcirculation. Systemic PAF conc entrations as found in shack could also compromise the cerebral microcircul ation. Our purpose in the present study was to examine the influence of sys temically applied PAF on microvascular perfusion and leukocyte-endothelium interactions in cerebral microvessels. Methods-A closed cranial window technique was used for intravital fluoresce nce microscopy of the brain surface. PAF was infused in concentrations of 1 0(-12), 10(-9), and 10(-6) mol/L into the carotid artery (5 mL/h for 20 min ) of Sprague-Dawley rats (n=30), The selective PAF receptor antagonist WEB 2170BS (2 mg/kg body weight) was used to inhibit specific PAF effects. Results-The number of leukocytes (cells/100 mu m min) rolling along or adhe ring at the venular endothelium increased following infusion of PAF 10(-6) mol/L from 7.7+/-2.5 to 24.4+/-8.9 (P<0.05) and from 1.9+/-0.5 to 6.9+/-2.2 (P<0.05), respectively, within 2 hours. Mean arterial pressure decreased f rom 92+/-22 mm Hg to 49+/-17 mm Hg (P<0.05). The lower concentrations of PA F were less effective to decrease mean arterial pressure but also induced l eukocyte-endothelium interactions. The intravenous administration of WEB 21 70BS 15 min before the infusion of PAF 10(-6) mol/L prevented both systemic hypotension and activation of leukocyte-endothelium interactions. Conclusions-Increased systemic blood levels of PAF as found during shock ca n not only cause systemic arterial hypotension but also induce leukocyte-en dothelium interactions in cerebral venules. The activation of leukocytes wa s found to be independent of PAF-induced arterial hypotension. The specific ity of these results is confirmed by the findings that WEB 2170BS could inh ibit the PAF-induced systemic hypotension as well as the activation of leuk ocytes.