Ward Natalie C, Puddey Ian B, Hodgson Jonathan M, Beilin Lawrence J, Croft Kevin D
School of Medicine and Pharmachology, University of Western Ausralia, Perth, Australia.
Free Radic Biol Med. 2005 Apr 15;38(8):1032-6. doi: 10.1016/j.freeradbiomed.2004.12.024.
Oxidative stress has been implicated in the pathogenesis of hypertension. 20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P450 product of arachidonic acid metabolism, thought to be involved in the regulation of blood pressure (BP). The metabolism of arachidonic acid by cytochrome P450 enzymes may be a significant source of oxidative stress. F2-isoprostanes are reliable markers of in vivo oxidative damage. gamma-Glutamyl transpeptidase (gamma-GT) has traditionally been associated with alcohol intake or liver dysfunction and may be an early marker of oxidative stress. The objective of the present study was to investigate relationships between 20-HETE excretion and markers of oxidative stress (F2-isoprostanes and gamma-GT). Sixty-nine treated hypertensive subjects underwent measurement of 24-h ambulatory BP, serum gamma-GT, and urinary F2-isoprostane and 20-HETE excretion. 20-HETE excretion was positively associated with 24-h diastolic BP (p = 0.005), alcohol intake (p = 0.008), gamma-GT (p = 0.007), and F2-isoprostanes (p = 0.005). F2-isoprostanes were positively associated with alcohol intake (p = 0.018) and gamma-GT (p = 0.01). In a multivariate regression, gamma-GT remained an independent predictor of 20-HETE excretion, after adjustment for age, gender, BMI, and alcohol intake. In conclusion, the study highlights the positive association observed between 20-HETE excretion and markers of oxidative damage. The study also provides evidence that gamma-GT may be a useful marker of oxidative stress.
氧化应激与高血压的发病机制有关。20-羟基二十碳四烯酸(20-HETE)是花生四烯酸代谢的细胞色素P450产物,被认为参与血压(BP)的调节。细胞色素P450酶对花生四烯酸的代谢可能是氧化应激的一个重要来源。F2-异前列腺素是体内氧化损伤的可靠标志物。γ-谷氨酰转肽酶(γ-GT)传统上与酒精摄入或肝功能障碍有关,可能是氧化应激的早期标志物。本研究的目的是调查20-HETE排泄与氧化应激标志物(F2-异前列腺素和γ-GT)之间的关系。69名接受治疗的高血压患者接受了24小时动态血压、血清γ-GT、尿F2-异前列腺素和20-HETE排泄的测量。20-HETE排泄与24小时舒张压(p = 0.005)、酒精摄入量(p = 0.008)、γ-GT(p = 0.007)和F2-异前列腺素(p = 0.005)呈正相关。F2-异前列腺素与酒精摄入量(p = 0.018)和γ-GT(p = 0.01)呈正相关。在多变量回归中,在调整年龄、性别、BMI和酒精摄入量后,γ-GT仍然是20-HETE排泄的独立预测因子。总之,该研究突出了20-HETE排泄与氧化损伤标志物之间的正相关关系。该研究还提供了证据表明γ-GT可能是氧化应激的一个有用标志物。