Yuhki K, Kashiwagi H, Kojima F, Kawabe J, Ushikubi F
Department of Pharmacology, Asahikawa Medical College, Asahikawa, Japan.
Int Angiol. 2010 Apr;29(2 Suppl):19-27.
The roles of prostanoids in the pathogenesis of cardiovascular diseases and in the development of pathological conditions have been examined using mice lacking the individual, specific prostanoid receptor. Prostaglandin (PG) I2 protected the heart from ischemia-reperfusion injury in a model of acute myocardial infarction. In addition, PGI2 suppressed the development of pressure overload-induced cardiac hypertrophy. Aside from its potent vasodilatory action, PGI2 contributed critically to the development of renovascular hypertension via the activation of the renin-angiotensin-aldosterone system. Thromboxane (TX) A2 and PGF2alpha were found to be the mediators of inflammatory tachycardia under a systemic inflammatory condition induced by lipopolysaccharide. Under a septic condition leading to a vascular hypo-responsive state, TXA2 worked to maintain vascular tone by inhibiting the induction of inducible nitric oxide synthase in vascular smooth muscle cells. Mice lacking the PGE2 receptor subtype EP3 had a bleeding tendency and were resistant to thromboembolism, due to a defective activation of platelets. From these studies, the important and novel roles of prostanoids in the pathogenesis of cardiovascular diseases have been clarified.
利用缺乏特定前列腺素受体的小鼠，研究了前列腺素在心血管疾病发病机制及病理状况发展中的作用。在急性心肌梗死模型中，前列腺素（PG）I2可保护心脏免受缺血再灌注损伤。此外，PGI2可抑制压力超负荷诱导的心脏肥大的发展。除了其强大的血管舒张作用外，PGI2通过激活肾素-血管紧张素-醛固酮系统，对肾血管性高血压的发展起关键作用。在脂多糖诱导的全身炎症状态下，血栓素（TX）A2和PGF2α被发现是炎症性心动过速的介质。在导致血管低反应状态的脓毒症情况下，TXA2通过抑制血管平滑肌细胞中诱导型一氧化氮合酶的诱导来维持血管张力。缺乏PGE2受体亚型EP3的小鼠由于血小板激活缺陷而有出血倾向且对血栓栓塞有抵抗力。通过这些研究，已阐明了前列腺素在心血管疾病发病机制中的重要且新颖的作用。
