Imig J D, Falck J R, Wei S, Capdevila J H
Department of Physiology, Tulane University School of Medicine, New Orleans, La., USA.
J Vasc Res. 2001 May-Jun;38(3):247-55. doi: 10.1159/000051053.
In the kidney, epoxyeicosatrienoic acids (EETs) have been suggested to be endothelium-derived hyperpolarizing factors (EDHFs). The aim of the present study was to determine the contribution of EETs to the preglomerular vasodilation elicited by bradykinin. Sprague-Dawley rats were studied utilizing an in vitro perfused juxtamedullary nephron preparation. The afferent arteriolar diameter was determined and the diameter averaged 19 +/- 1 microm (n = 26) at a renal perfusion pressure of 100 mm Hg. Addition of 1, 10 and 100 nM bradykinin to the perfusate dose-dependently increased afferent arteriolar diameter by 5 +/- 1, 12 +/- 2 and 17 +/- 2%, respectively. The nitric oxide inhibitor N(omega)-nitro-L-arginine reduced bradykinin-induced afferent arteriolar vasodilation by 50%, and the diameter increased by 9 +/- 2% in response to 100 nM bradykinin. Epoxygenase inhibitors N-methylsulphonyl-6-(2-propargyloxyphenyl)hexanamide or miconazole greatly attenuated the nitric oxide-independent component of the vasodilation elicited by bradykinin. Cyclooxygenase (COX) inhibition attenuated the nitric oxide-independent vasodilation elicited by 1 nM bradykinin but did not significantly affect the vascular response to 100 nM bradykinin. Combined inhibition of nitric oxide, COX and epoxygenase pathways completely abolished bradykinin-mediated afferent arteriolar vasodilation. In additional studies, renal microvessels were isolated and incubated with bradykinin and samples were analyzed by NICI/GC/MS. Under control conditions, renal microvascular EET levels averaged 49 +/- 9 pg/mg/20 min (n = 7). In the presence of bradykinin, EET levels were significantly higher and averaged 81 +/- 11 pg/mg/20 min (n = 7). These data support the concept that EETs are EDHFs and contribute to the nitric oxide-independent afferent arteriolar vasodilation elicited by bradykinin.
在肾脏中，环氧二十碳三烯酸（EETs）被认为是内皮衍生的超极化因子（EDHFs）。本研究的目的是确定EETs在缓激肽引起的肾小体前血管舒张中的作用。利用体外灌注的近髓肾单位制备方法对Sprague-Dawley大鼠进行研究。测定传入小动脉直径，在100 mmHg肾灌注压下，平均直径为19±1微米（n = 26）。向灌注液中添加1、10和100 nM缓激肽，分别使传入小动脉直径剂量依赖性增加5±1%、12±2%和17±2%。一氧化氮抑制剂N（ω）-硝基-L-精氨酸使缓激肽诱导的传入小动脉血管舒张减少50%，在100 nM缓激肽作用下，直径增加9±2%。环氧合酶抑制剂N-甲基磺酰基-6-（2-炔丙氧基苯基）己酰胺或咪康唑大大减弱了缓激肽引起的血管舒张的一氧化氮非依赖性成分。环氧化酶（COX）抑制减弱了1 nM缓激肽引起的一氧化氮非依赖性血管舒张，但对血管对100 nM缓激肽的反应无显著影响。一氧化氮、COX和环氧合酶途径的联合抑制完全消除了缓激肽介导的传入小动脉血管舒张。在额外的研究中，分离肾微血管并用缓激肽孵育，样品通过NICI/GC/MS分析。在对照条件下，肾微血管EET水平平均为49±9 pg/mg/20分钟（n = 7）。在缓激肽存在下，EET水平显著升高，平均为81±11 pg/mg/20分钟（n = 7）。这些数据支持EETs是EDHFs并参与缓激肽引起的一氧化氮非依赖性传入小动脉血管舒张的概念。
