Imig John D
Vascular Biology Center, Department of Physiology, Medical College of Georgia, Augusta, GA 30912, USA.
Clin Sci (Lond). 2006 Jul;111(1):21-34. doi: 10.1042/CS20050251.
Arachidonic acid metabolites are vital for the proper control of renal haemodynamics and, when not properly controlled, can contribute to renal vascular injury and end-stage renal disease. Three major enzymatic pathways, COX (cyclo-oxygenase), CYP450 (cytochrome P450) and LOX (lipoxygenase), are responsible for the metabolism of arachidonic acid metabolites to bioactive eicosanoids. These eicosanoids can dilate or constrict the renal vasculature and maintain vascular resistance in the face of changing vasoactive hormones. Renal vascular generation of eicosanoids is altered in pathophysiological conditions such as hypertension, diabetes, metabolic syndrome and acute renal failure. Experimental evidence supports the concept that altered eicosanoid metabolism contributes to renal haemodynamic alterations and the development and progression of nephropathy. The possible beneficial renal vascular actions of enzymatic inhibitors, eicosanoid analogues and receptor antagonists have been examined in hypertension, diabetes and metabolic syndrome. This review highlights the roles of renal vascular eicosanoids in the pathogenesis of nephropathy and therapeutic targets for renal disease related to hypertension, diabetes, metabolic syndrome and acute renal failure.
花生四烯酸代谢产物对于肾脏血流动力学的正常调控至关重要，若调控不当，可导致肾血管损伤和终末期肾病。花生四烯酸代谢产物通过三条主要的酶促途径代谢为具有生物活性的类二十烷酸，这三条途径分别是COX（环氧化酶）、CYP450（细胞色素P450）和LOX（脂氧合酶）。这些类二十烷酸可使肾血管舒张或收缩，并在血管活性激素变化时维持血管阻力。在高血压、糖尿病、代谢综合征和急性肾衰竭等病理生理状态下，肾脏血管生成类二十烷酸的过程会发生改变。实验证据支持这样的观点，即类二十烷酸代谢改变会导致肾脏血流动力学改变以及肾病的发生和发展。在高血压、糖尿病和代谢综合征中，人们已经研究了酶抑制剂、类二十烷酸类似物和受体拮抗剂对肾脏血管可能的有益作用。本综述重点介绍了肾脏血管类二十烷酸在肾病发病机制中的作用，以及与高血压、糖尿病、代谢综合征和急性肾衰竭相关的肾脏疾病的治疗靶点。
