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

本文研究了肾素-血管紧张素系统(RA)和血栓素A_2(T_2)、血栓素(T_X)在降低肾灌流压时维持肾循环中的作用。在肾动脉压(RAP)降至60毫米汞柱前和降至60毫米汞柱时，观察RA系统与~lt；TXA_2和Gt；的相互作用。当平均肾动脉压降至60毫米汞柱时，肾动脉内注射血管紧张素II(A-II)可降低RBF，但增加GFR。相反，在正常RAP时，A-II输注后的RBF和GFR的变化与未治疗的狗相似，但在减少RAP A-II输注期间，用&lt；TXA2&Gt；合成酶抑制剂UK-38485处理的狗的GFR下降。低灌注组大鼠肾皮质分泌的&lt；TXB_2和Gt；含量为正常RAP时的2.7倍。然而，卡托普利处理的肾脏在减少RAP的过程中并没有增加&lt；TXB_2&gt；的产生。这些结果表明，RA系统和前列腺素类物质，尤其是&lt；TXA2和Gt；是维持低RAP下GFR的重要因素。去乙酰胆碱酯酶(CA)可使高动力状态消失。LTS拮抗剂(FPL)能部分拮抗CA耗竭大鼠的低血压。FPL联合血小板活化因子(PAF)拮抗剂(CV-3988)可抑制脂多糖诱导的微血管通透性改变，提高存活率。上述结果提示，抑制LTS和PAF活性对休克的治疗有一定作用。

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.