DeFily D V, Kuo L, Chilian W M
Department of Medical Physiology, Texas A & M University Health Science Center, College Station 77843-1114, USA.
Am J Physiol. 1996 Jun;270(6 Pt 2):H2094-9. doi: 10.1152/ajpheart.1996.270.6.H2094.
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.
据报道，血小板活化因子（PAF）在多种血管制剂中，对中性粒细胞活化、微血管通透性及内皮功能障碍发挥作用。虽然PAF的大部分作用被认为是由中性粒细胞的活化介导的，但PAF的有害作用在多大程度上扩展至冠状动脉阻力血管尚不清楚。因此，本研究的目的是确定PAF在体内是否会导致冠状动脉小动脉内皮功能障碍，以及这种功能障碍是否独立于活化的中性粒细胞。为了验证这些假设，我们在冠状动脉内注入PAF（20 ng·kg⁻¹·min⁻¹）后，通过活体显微镜测量跳动犬心脏的冠状动脉微血管直径，来测定体内冠状动脉小动脉直径对内皮依赖性和非依赖性扩张剂的变化。在分离的冠状动脉小动脉中也测量了与PAF孵育后冠状动脉小动脉直径的变化。在体内，与PAF孵育导致对冠状动脉内乙酰胆碱（0.1 μg·kg⁻¹·min⁻¹，扩张39±7%对20±3%）和5-羟色胺（1 μg·kg⁻¹·min⁻¹，扩张29±6%对2±2%）的内皮依赖性扩张显著减弱。然而，罂粟碱诱导的舒张未改变。同样，在体外，用PAF处理后对5-羟色胺（10 nM）的舒张显著降低（38±4%对3±5%），而硝普钠（10 nM）诱导的舒张未改变。由于PAF在体内和体外均损害了内皮依赖性小动脉扩张，我们得出结论，PAF诱导的冠状动脉微血管功能障碍不需要活化的中性粒细胞存在。
