Marji Jackleen S, Wang Mong-Heng, Laniado-Schwartzman Michal
Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA.
Am J Physiol Renal Physiol. 2002 Jul;283(1):F60-7. doi: 10.1152/ajprenal.00265.2001.
20-Hydroxyeicosatetraenoic acid (20-HETE), a potent vasoconstrictor and mediator of the myogenic response, is a major arachidonic acid metabolite in the microvasculature of the rat kidney formed primarily by the cytochrome P-450 (CYP) 4A isoforms, CYP4A1, CYP4A2, and CYP4A3. We examined CYP4A isoform expression and 20-HETE synthesis in microdissected interlobar, arcuate, and interlobular arteries; mRNA for all CYP4A isoforms was identified by RT-PCR. Western blot analysis indicated that the levels of CYP4A2/4A3-immunoreactive protein increased with decreased arterial diameter, whereas those of CYP4A1-immunoreactive protein remained unchanged. 20-HETE synthesis was the highest in the interlobular arteries (17 +/- 1.62 nmol. mg(-1). h(-1)) and, like CYP4A2/4A3-immunoreactive protein, decreased with increasing vessel diameter (4.5 +/- 1.21, 2.65 +/- 0.58, and 0.81 +/- 0.14 nmol. mg(-1). h(-1) in the arcuate, interlobar, and segmental arteries, respectively). 20-HETE synthesis in the renal artery and the abdominal aorta was undetectable. The observed decreased immunoreactivity of NADPH-cytochrome P-450 (c) oxidoreductase with increased arterial diameter provided a possible explanation for the decreased capacity to generate 20-HETE in the large arteries. The increase in CYP4A isoform expression and 20-HETE synthesis with decreasing diameter along the preglomerular arteries and the potent biological activity of 20-HETE underscore the significance of 20-HETE as a modulator of renal hemodynamics.
20-羟基二十碳四烯酸（20-HETE）是一种强效血管收缩剂和肌源性反应介质，是大鼠肾脏微血管中主要的花生四烯酸代谢产物，主要由细胞色素P-450（CYP）4A亚型CYP4A1、CYP4A2和CYP4A3形成。我们检测了显微解剖的叶间动脉、弓形动脉和小叶间动脉中CYP4A亚型的表达及20-HETE的合成；通过逆转录聚合酶链反应（RT-PCR）鉴定了所有CYP4A亚型的信使核糖核酸（mRNA）。蛋白质免疫印迹分析表明，CYP4A2/CYP4A3免疫反应性蛋白水平随动脉直径减小而升高，而CYP4A1免疫反应性蛋白水平保持不变。20-HETE合成在小叶间动脉中最高（17±1.62 nmol·mg⁻¹·h⁻¹），并且与CYP4A2/CYP4A3免疫反应性蛋白一样，随血管直径增加而降低（在弓形动脉、叶间动脉和段动脉中分别为4.5±1.21、2.65±0.58和0.81±0.14 nmol·mg⁻¹·h⁻¹）。肾动脉和腹主动脉中未检测到20-HETE合成。观察到的烟酰胺腺嘌呤二核苷酸磷酸-细胞色素P-450（c）氧化还原酶免疫反应性随动脉直径增加而降低，为大动脉中生成20-HETE能力降低提供了一种可能的解释。沿肾小体前动脉CYP4A亚型表达和20-HETE合成随直径减小而增加，以及20-HETE的强大生物活性，突出了20-HETE作为肾血流动力学调节剂的重要性。
