title: PAF attenuates endothelium-dependent coronary arteriolar vasodilation.
abstract: Platelet-activating factor (PAF) has been reported to play a role in neutrophil activation, microvascular permeability, and endothelial dysfunction in a variety of vascular preparations. Although a majority of the effects of PAF are thought to be mediated by the activation of neutrophils, it is unclear the extent to which the deleterious effects of PAF extend to coronary resistance vessels. Therefore, the purpose of this study was to determine whether PAF causes coronary arteriolar endothelial dysfunction in vivo and whether this dysfunction is independent of activated neutrophils. To test these hypotheses, we measured changes in coronary arteriolar diameter to endothelium-dependent and -independent dilators in vivo by measuring coronary microvascular diameters in a beating canine heart using intravital videomicroscopy following intracoronary infusion of PAF (20 ng.kg-1.min-1). Changes in coronary arteriolar diameter following incubation with PAF were also measured in isolated coronary arterioles. In vivo, incubation with PAF resulted in a significant attenuation of endothelium-dependent dilation to intracoronary acetylcholine (0.1 microgram.kg-1.min-1, 39 +/- 7 vs. 20 +/- 3% dilation) and serotonin (1 microgram.kg-1.min-1, 29 +/- 6 vs. 2 +/- 2% dilation). Papaverine-induced relaxation, however, was unchanged. Likewise, in vitro relaxation to serotonin (10 nM) was significantly reduced (38 +/- 4 vs. 3 +/- 5%) following treatment with PAF, whereas nitroprusside (10 nM)-induced relaxation was unchanged. Because PAF impaired endothelium-dependent arteriolar dilation both in vivo and in vitro, we conclude that the presence of activated neutrophils is not required for PAF-induced coronary microvascular dysfunction.
authors.affiliation: Department of Medical Physiology, Texas A & M University Health Science Center, College Station 77843-1114, USA.
authors.forename: D V
authors.initials: DV
authors.lastname: DeFily
authors.forename: L
authors.initials: L
authors.lastname: Kuo
authors.forename: W M
authors.initials: WM
authors.lastname: Chilian
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction; D009599:Nitroprusside / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D010972:Platelet Activating Factor; D014665:Vasodilator Agents; D009599:Nitroprusside; D012701:Serotonin; D000109:Acetylcholine