The role of arachidonic acid cascade as a autacoid in hypoperfused vital organs

本文研究了肾灌注压降低时，肾循环维持过程中肾素-血管紧张素（RA）系统和血栓素（TX）的作用<A_2>。在<TXA_2>肾动脉压（RAP）降至60 mmHg之前和期间，检查RA系统与RA之间的相互作用。肾动脉内注射血管紧张素II（A-II）可降低肾动脉压（60 mmHg）时的RBF，但增加GFR。相反，A-II输注后RBF和GFR的变化与正常RAP下未治疗犬相似，但在减少RAP A-II输注期间，<TXA_2>合成酶抑制剂UK-38485预处理犬的GFR降低。低<TXB_2>灌注肾皮质的产量增加到正常RAP的2.7倍。然而，<TXB_2>生产并没有增加减少RAP在卡托普利预处理的肾脏。提示RA系统和前列腺素类<TXA_2>是维持低RAP GFR的重要因素。本文研究了内毒素休克时白三烯（LT）和儿茶酚胺（CA）的相互作用。大肠杆菌脂多糖（LPS）给药后的高动力状态通过CA的消耗而消失。LTs拮抗剂（FPL）部分拮抗CA缺失大鼠给予LPS后的低血压。FPL联合血小板活化因子（PAF）拮抗剂CV-3988预处理可抑制LPS致微血管通透性的改变，提高存活率。这些结果表明，抑制LTs和PAF活性对休克的治疗是有益的。

The role of renin-angiotensin(RA) system and thromboxane(TX) <A_2> on maintenance of renal circulation during reduced renal perfusion pressure was studied in dogs. The interaction between RA system and <TXA_2> was examined, before and during the renal artery pressure(RAP) was decreased to 60 mmHg. Intrarenal arterial administration of angiotensin II(A-II) reduced RBF, but increased GFR, when mean renal arterial pressure was decreased to 60mmHg. On the contrary, the changes of RBF and GFR following A-II infusion were similar to non-treated dogs at normal RAP, but during reduced RAP A-II infusion decreased GFR in dogs pretreated with <TXA_2> synthetase inhibitor, UK-38485. The <TXB_2> production by renal cortex in hypoperfused kidney increased to 2.7 fold of that at normal RAP. However, <TXB_2> production did not increase during reduced RAP in captopril pretreated kidney. These results suggest that RA system and prostanoids, especially <TXA_2> , are essential factor to maintain GFR at low RAP.The interaction of leukotriene(LT) and catecholamine(CA) in endotoxin shock was studied in rats. Hyperdynamic state following E.coli lipopolisaccaride(LPS) administration was disappeared by depletion of CA. LTs antagonist(FPL) antagonized the hypotension partially following LPS administration in CA depleted rats. Pretreatment of FPL combined with platelet activating factor(PAF) antagonist(CV-3988) inhibited the change of microvascular permeability following LPS administration, and increased survival rate. These results suggest that the inhibition of LTs and PAF activity is useful for the treatment of shock.