Cheng Monica K, McGiff John C, Carroll Mairead A
Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA.
Am J Physiol Renal Physiol. 2003 Mar;284(3):F474-9. doi: 10.1152/ajprenal.00239.2002. Epub 2002 Nov 5.
20-HETE, a potent vasoconstrictor, is generated by cytochrome P-450 omega-hydroxylases and is the principal eicosanoid produced by preglomerular microvessels. It is released from preglomerular microvessels by ANG II and is subject to metabolism by cyclooxygenase (COX). Because low-salt (LS) intake stimulates the renin-angiotensin system and induces renal cortical COX-2 expression, we examined 20-HETE release from renal arteries (interlobar and arcuate and interlobular arteries) obtained from 6- to 7-wk-old male Sprague-Dawley rats fed either normal salt (0.4% NaCl) or LS (0.05% NaCl) diets for 10 days. With normal salt intake, the levels of 20-HETE recovered were similar in arcuate and interlobular arteries and interlobar arteries: 30.1 +/- 8.5 vs. 24.6 +/- 5.3 ng. mg protein(-1). 30 min(-1), respectively. An LS diet increased 20-HETE levels in the incubate of either arcuate and interlobular or interlobar renal arteries only when COX was inhibited. Addition of indomethacin (10 microM) to the incubate of arteries obtained from rats fed an LS diet resulted in a two- to threefold increase in 20-HETE release from arcuate and interlobular arteries, from 39.1 +/- 13.2 to 101.8 +/- 42.6 ng. mg protein(-1). 30 min(-1) (P < 0.03), and interlobar arteries, from 31.7 +/- 15.1 to 61.9 +/- 29.4 ng. mg protein(-1). 30 min(-1) (P < 0.05) compared with release of 20-HETE when COX was not inhibited. An LS diet enhanced vascular expression of cytochrome P-4504A and COX-2 in arcuate and interlobular arteries; COX-1 was unaffected. Metabolism of 20-HETE by COX is proposed to represent an important regulatory mechanism in setting preglomerular microvascular tone.
20-羟基二十碳四烯酸（20-HETE）是一种强效血管收缩剂，由细胞色素P-450 ω-羟化酶生成，是球前微血管产生的主要类花生酸。它由血管紧张素II（ANG II）从球前微血管释放，并受环氧化酶（COX）代谢。由于低盐（LS）摄入会刺激肾素-血管紧张素系统并诱导肾皮质COX-2表达，我们检测了从6至7周龄雄性Sprague-Dawley大鼠获取的肾动脉（叶间动脉、弓状动脉和小叶间动脉）中20-HETE的释放情况，这些大鼠分别喂食正常盐（0.4% NaCl）或LS（0.05% NaCl）饮食10天。在正常盐摄入情况下，弓状动脉、小叶间动脉和叶间动脉中回收的20-HETE水平相似：分别为30.1±8.5 ng·mg蛋白⁻¹·30 min⁻¹和24.6±5.3 ng·mg蛋白⁻¹·30 min⁻¹。仅当COX受到抑制时，LS饮食才会增加弓状动脉和小叶间动脉或叶间肾动脉孵育液中的20-HETE水平。向喂食LS饮食的大鼠获取的动脉孵育液中添加吲哚美辛（10 μM），导致弓状动脉和小叶间动脉中20-HETE释放增加两到三倍，从39.1±13.2 ng·mg蛋白⁻¹·30 min⁻¹增加到101.8±42.6 ng·mg蛋白⁻¹·30 min⁻¹（P<0.03），叶间动脉从31.7±15.1 ng·mg蛋白⁻¹·30 min⁻¹增加到61.9±29.4 ng·mg蛋白⁻¹·30 min⁻¹（P<0.05），与未抑制COX时20-HETE的释放相比。LS饮食增强了弓状动脉和小叶间动脉中细胞色素P-4504A和COX-2的血管表达；COX-1未受影响。COX对20-HETE的代谢被认为是调节球前微血管张力的一种重要调控机制。
