Ma Y H, Dunham E W
Department of Pharmacology, Medical School, University of Minnesota, Minneapolis 55455.
Eur J Pharmacol. 1988 Jan 12;145(2):153-62. doi: 10.1016/0014-2999(88)90226-9.
The hemodynamic effects of platelet activating factor (PAF), PAF antagonists and a precursor of PAF, 1-palmityl-2-acetyl-glycerol (PAG), were examined in pentobarbital-anesthetized spontaneously hypertensive rats to determine whether functionally significant amounts of PAF are produced via the cholinephosphotransferase pathway of PAF synthesis in vivo. Intravenous bolus doses of PAF, PAG and nitroprusside elicited hypotension and active mesenteric vasodilatation. Responses to PAG were slower in onset and longer in duration than those of PAF and nitroprusside. The specific PAF antagonists, CV-3988 and SRI 63-675, attenuated PAG- and PAF-, but not nitroprusside-induced changes in blood pressure and mesenteric flow/resistance. In contrast, captopril, which blocked the effects of angiotensin I, did not influence the hypotension caused by PAG, PAF and nitroprusside. The results suggest that the vasodilator effects of PAG are attributable to PAF produced from this alkylacetylglycerol, and the renin-angiotensin system does not appear to influence the biotransformation of PAG to PAF or the hypotensive action of PAF.
在戊巴比妥麻醉的自发性高血压大鼠中，研究了血小板活化因子（PAF）、PAF拮抗剂以及PAF的前体1-棕榈酰-2-乙酰甘油（PAG）的血流动力学效应，以确定体内是否通过PAF合成的胆碱磷酸转移酶途径产生了具有功能意义的PAF量。静脉推注PAF、PAG和硝普钠可引起低血压和肠系膜血管主动扩张。PAG引起的反应起效较慢且持续时间较长，与PAF和硝普钠引起的反应不同。特异性PAF拮抗剂CV-3988和SRI 63-675可减弱PAG和PAF引起的血压和肠系膜血流/阻力变化，但对硝普钠引起的变化无影响。相比之下，阻断血管紧张素I作用的卡托普利对PAG、PAF和硝普钠引起的低血压无影响。结果表明，PAG的血管舒张作用归因于由这种烷基乙酰甘油产生的PAF，肾素-血管紧张素系统似乎不影响PAG向PAF的生物转化或PAF的降压作用。
