Imig J D
Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Am J Physiol Renal Physiol. 2000 Dec;279(6):F965-81. doi: 10.1152/ajprenal.2000.279.6.F965.
Even though it has been recognized that arachidonic acid metabolites, eicosanoids, play an important role in the control of renal blood flow and glomerular filtration, several key observations have been made in the past decade. One major finding was that two distinct cyclooxygenase (COX-1 and COX-2) enzymes exist in the kidney. A renewed interest in the contribution of cyclooxygenase metabolites in tubuloglomerular feedback responses has been sparked by the observation that COX-2 is constitutively expressed in the macula densa area. Arachidonic acid metabolites of the lipoxygenase pathway appear to be significant factors in renal hemodynamic changes that occur during disease states. In particular, 12(S)- hydroxyeicosatetraenoic acid may be important for the full expression of the renal hemodynamic actions in response to angiotensin II. Cytochrome P-450 metabolites have been demonstrated to possess vasoactive properties, act as paracrine modulators, and be a critical component in renal blood flow autoregulatory responses. Last, peroxidation of arachidonic acid metabolites to isoprostanes appears to be involved in renal oxidative stress responses. The recent developments of specific enzymatic inhibitors, stable analogs, and gene-disrupted mice and in antisense technology are enabling investigators to understand the complex interplay by which eicosanoids control renal blood flow.
尽管人们已经认识到花生四烯酸代谢产物（类二十烷酸）在肾血流控制和肾小球滤过中发挥着重要作用，但在过去十年中仍有一些关键发现。一个主要发现是，肾脏中存在两种不同的环氧化酶（COX - 1和COX - 2）。观察到COX - 2在致密斑区域组成性表达，这引发了人们对环氧化酶代谢产物在肾小管 - 肾小球反馈反应中作用的新兴趣。脂氧合酶途径的花生四烯酸代谢产物似乎是疾病状态下发生的肾血流动力学变化的重要因素。特别是，12(S)-羟基二十碳四烯酸对于在血管紧张素II作用下肾血流动力学作用的充分表达可能很重要。细胞色素P - 450代谢产物已被证明具有血管活性特性，可作为旁分泌调节剂，并且是肾血流自身调节反应的关键组成部分。最后，花生四烯酸代谢产物过氧化生成异前列腺素似乎参与了肾氧化应激反应。特异性酶抑制剂、稳定类似物、基因敲除小鼠以及反义技术的最新进展使研究人员能够了解类二十烷酸控制肾血流的复杂相互作用。
