Li Jing, Carroll Mairead A, Chander Praveen N, Falck John R, Sangras Bhavani, Stier Charles T
Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA.
Front Biosci. 2008 May 1;13:3480-7. doi: 10.2741/2942.
In stroke-prone spontaneously hypertensive rats (SHRSP) end-organ damage is markedly accelerated by high-salt (HS) intake. Since epoxyeicosatrienoic acids (EETs) possess vasodepressor and natriuretic activities, we examined whether a soluble epoxide hydrolase (sEH) inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), to inhibit the metabolism of EETs, would protect against pathologic changes in SHRSP. Seven-week-old male SHRSP were treated as follows: normal salt (NS), NS + AUDA, HS and HS + AUDA. Systolic blood pressure (SBP) (205 +/- 4 v 187 +/- 7 mmHg) and proteinuria (3.7 +/- 0.2 v 2.6 +/- 0.2 mg/6 h), but not plasma EETs (11.0 +/- 0.9 v 9.7 +/- 1.1 ng/ml), were significantly increased at 9 weeks of age in HS v NS SHRSP. HS was associated with fibrinoid degeneration and hypertrophy of arterioles in the kidney and perivascular fibrosis and contraction band necrosis in the heart. AUDA ameliorated these early salt-dependent changes in saline-drinking SHRSP and increased plasma levels of EETs but did not affect water and electrolyte excretion. sEH inhibition may provide a therapeutic strategy for treating salt-sensitive hypertension and its sequelae.
在易患中风的自发性高血压大鼠（SHRSP）中，高盐（HS）摄入会显著加速终末器官损伤。由于环氧二十碳三烯酸（EETs）具有血管舒张和利钠活性，我们研究了一种可溶性环氧化物水解酶（sEH）抑制剂12-（3-金刚烷-1-基-脲基）-十二烷酸（AUDA）抑制EETs代谢是否能预防SHRSP的病理变化。将7周龄雄性SHRSP按以下方式处理：正常盐（NS）、NS + AUDA、HS和HS + AUDA。与NS组SHRSP相比，HS组SHRSP在9周龄时收缩压（SBP）（205±4对187±7 mmHg）和蛋白尿（3.7±0.2对2.6±0.2 mg/6 h）显著升高，但血浆EETs水平（11.0±0.9对9.7±1.1 ng/ml）无显著差异。HS与肾脏小动脉的纤维蛋白样变性和肥大以及心脏的血管周围纤维化和收缩带坏死有关。AUDA改善了饮用盐水的SHRSP中这些早期盐依赖性变化，并提高了血浆EETs水平，但不影响水和电解质排泄。抑制sEH可能为治疗盐敏感性高血压及其后遗症提供一种治疗策略。
