González-Núñez D, Claria J, Rivera F, Poch E
Servicio de Nefrología, Laboratorio de Hormonología (D.G.-N., F.R.), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain.
Hypertension. 2001 Feb;37(2):334-8. doi: 10.1161/01.hyp.37.2.334.
The platelet-type 12-lipoxygenase (12-LO) catalyzes the transformation of arachidonic acid into 12-hydroperoxyeicosatetraenoic acid [12-(S)HPETE], which is reduced to 12-hydroxyeicosatetraenoic acid [12-(S)HETE]. These metabolites exhibit a variety of biological activities such as mediation of angiotensin II-induced intracellular calcium transients in cultured rat vascular smooth muscle cells. It has recently been reported that platelet 12(S)-HETE production is enhanced in the spontaneously hypertensive rat. The pronounced hypotensive effect of LO inhibition in SHR suggests that LO activity may play a role in this form of hypertension. The aim of this study was to determine the basal and thrombin-induced platelet 12(S)-HETE production and the urinary 12(S)-HETE excretion in essential hypertension. We studied 19 patients with this disease (57+/-2 years of age) and 9 normotensive control subjects (48+/-5 years of age) (P:=0.074). 12(S)-HETE was measured in Sep-Pack-extracted samples with specific ELISA and high-performance liquid chromatography. The platelet basal level of 12(S)-HETE was significantly higher in patients than in control subjects (3.56+/-1.22 versus 0.64+/-0.13 ng/10(6) platelets, P:<0.025). In contrast, there were no differences in thrombin-stimulated (1 U/mL) 12(S)-HETE generation: 7.66+/-2.14 in patients versus 4.87+/-1.46 in control subjects (P:=0.61). Platelet 12-LO protein levels, measured by Western blotting with a polyclonal antibody, were higher in the patients than in the control subjects. The urinary excretion of 12(S)-HETE was higher in patients than in control subjects: 36.8+/-7.24 versus 17.1+/-3.14 ng/mg creatinine (P:<0.01). These results indicate that 12(S)-HETE levels and 12-LO protein are increased in patients with essential hypertension, suggesting a role for this metabolite in human hypertension.
血小板型12 - 脂氧合酶（12 - LO）催化花生四烯酸转化为12 - 氢过氧二十碳四烯酸[12 - （S）HPETE]，后者再还原为12 - 羟基二十碳四烯酸[12 - （S）HETE]。这些代谢产物具有多种生物学活性，如在培养的大鼠血管平滑肌细胞中介导血管紧张素II诱导的细胞内钙瞬变。最近有报道称，自发性高血压大鼠血小板12（S） - HETE的生成增加。在自发性高血压大鼠中，脂氧合酶抑制具有显著的降压作用，这表明脂氧合酶活性可能在这种高血压形式中起作用。本研究的目的是测定原发性高血压患者基础状态下及凝血酶诱导的血小板12（S） - HETE生成情况以及尿中12（S） - HETE的排泄情况。我们研究了19例该疾病患者（年龄57±2岁）和9名血压正常的对照者（年龄48±5岁）（P = 0.074）。采用特异性酶联免疫吸附测定法（ELISA）和高效液相色谱法测定Sep - Pack提取样品中的12（S） - HETE。患者血小板12（S） - HETE的基础水平显著高于对照者（3.56±1.22对0.64±0.13 ng/10⁶个血小板，P < 0.025）。相比之下，凝血酶刺激（浓度为1 U/mL）后12（S） - HETE的生成量在患者和对照者之间没有差异：患者为7.66±2.14，对照者为4.87±1.46（P = 0.61）。用多克隆抗体通过蛋白质印迹法测定的血小板12 - LO蛋白水平，患者高于对照者。患者尿中12（S） - HETE的排泄量高于对照者：36.8±7.24对17.1±3.14 ng/mg肌酐（P < 0.01）。这些结果表明，原发性高血压患者12（S） - HETE水平和12 - LO蛋白增加，提示该代谢产物在人类高血压中起作用。
