| pubmed-article:2261677 | pubmed:abstractText | We have compared the cardiovascular effect of endotoxin with platelet-activating factor (PAF) in rats. Endotoxin injected into perfusate of isolated rat heart did not induce significant changes in heart function, whereas PAF induced elevation of coronary perfusion pressure (CPP), decrease in ventricular pressure (VP), decrease in coronary flow (CF), but no significant changes in heart rate (HR). Neither endotoxin nor PAF caused contraction or relaxation of isolated rat arteries. However, endotoxin in the presence of macrophages caused contractions of rat aortic strips. These contractions were potentiated when platelets were present in the macrophage preparation. PAF in the presence of platelets caused profound contraction of the aortic strips, and this action of PAF was entirely blocked by either PAF antagonists or thromboxane antagonists. Injection of endotoxin into rats (i.v.) caused a decrease in blood pressure (BP) without significantly affecting the HR. At higher concentrations (greater than or equal to 10 mg/kg), endotoxin caused ventricular tachycardia (VT) associated with ventricular fibrillation (VF). PAF in vivo caused a rapid and sustained decrease in BP, with an ED50 of 3 micrograms/kg. PAF antagonists significantly prevented overall mortality induced by PAF and short-term endotoxin-induced mortality, but not the long-term (week) mortality. Endotoxin (10 mg/kg) injected into rats caused the release of PAF into the circulation, reaching a maximum after 2-5 min. Tritiated PAF injected into rats i.v. was metabolized over 60 min into lyso-PAF (approximately 30%), acyl-PAF (approximately 10%), and some degraded products (approximately 10%), and the remainder was found in the form of PAF. The results of the present study suggest that PAF may play a significant role in the pathogenesis of endotoxin shock. The action of PAF requires the participation of cells such as platelets, macrophages, neutrophils, and monocytes and involvement of arachidonic acid metabolites. | lld:pubmed |
