Kamitani T, Katamoto M, Tatsumi M, Katsuta K, Ono T, Kikuchi H, Kumada S
Eur J Pharmacol. 1984 Mar 2;98(3-4):357-66. doi: 10.1016/0014-2999(84)90284-x.
The mechanism of the hypotensive effect of 1-O-octadecyl-2-O-acetyl-glycero-3-phosphorylcholine (C18- AGPC ) was examined. Synthetic C18- AGPC caused dose-dependent hypotension in conscious rats. The activity was almost the same in DOCA and renal hypertensive rats. This suggests that it is not a renin inhibitor. Hypotension also appeared in pithed rats. This suggests that the effect is not due to a central mechanism. Hypotension did not result from platelet aggregation or bronchial constriction. Since C18- AGPC suppressed not only the pressor response to noradrenaline but also to angiotensin II and vasopressin, and furthermore, did not disturb the dose-response curve of noradrenaline in the isolated aorta, the possibility of the agent being an alpha-adrenergic antagonist is ruled out. In the PGF2 alpha-contracted rat aorta. C18- AGPC caused marked vasodilation, which disappeared after removal of the endothelium. Perfusion pressure decreased in the blood-perfused rat hindquarters but not in the Tyrode solution-perfused ones. C18- AGPC induced a positive inotropic effect in isolated rat atrium. The hypotensive effect of synthetic C18- AGPC seems to be mainly due to endothelium-dependent vasodilation.
研究了1-O-十八烷基-2-O-乙酰基甘油-3-磷酸胆碱（C18-AGPC）的降压作用机制。合成的C18-AGPC在清醒大鼠中引起剂量依赖性低血压。在去氧皮质酮（DOCA）和肾性高血压大鼠中，该活性几乎相同。这表明它不是一种肾素抑制剂。在脊髓切断的大鼠中也出现了低血压。这表明该作用不是由中枢机制引起的。低血压不是由血小板聚集或支气管收缩导致的。由于C18-AGPC不仅抑制了对去甲肾上腺素的升压反应，还抑制了对血管紧张素II和血管加压素的反应，而且在离体主动脉中不干扰去甲肾上腺素的剂量反应曲线，因此排除了该药物是α-肾上腺素能拮抗剂的可能性。在前列腺素F2α收缩的大鼠主动脉中，C18-AGPC引起明显的血管舒张，在内皮去除后消失。在血液灌注的大鼠后肢中灌注压力降低，但在台氏液灌注的后肢中未降低。C18-AGPC在离体大鼠心房中诱导了正性肌力作用。合成的C18-AGPC的降压作用似乎主要归因于内皮依赖性血管舒张。
