Department of Physiology, College of Medicine, Chosun University, Gwangju, Korea.
Department of Psychiatry, College of Medicine, Chosun University, Gwangju, Korea.
Kidney Res Clin Pract. 2014 Mar;33(1):19-25. doi: 10.1016/j.krcp.2013.12.001. Epub 2014 Feb 14.
Endothelial dysfunction is linked to exaggerated production of superoxide anions. This study was conducted to examine the effects of oxidative stress on endothelial modulation of contractions in chronic two-kidney, one-clip (2K1C) renal hypertensive rats.
The 2K1C hypertension was induced by clipping the left renal artery; age-matched rats receiving sham treatment served as controls. Thoracic aortae were isolated and mounted in tissue baths for measurement of isometric tension.
Norepinephrine-induced contraction was augmented by the removal of the endothelium, which was more pronounced in sham rats than in 2K1C rats. Nω-nitro-L-arginine methyl ester, an inhibitor of nitric oxide production, had a similar augmenting effect. Vitamin C inhibited the contraction in aortic rings with intact endothelium from 2K1C rats but not from sham rats. The contraction was also suppressed by treatment with diphenyleneiodonium or apocynin, inhibitors of nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase, in the aortae with intact endothelium from 2K1C rats but not in those from sham rats. Superoxide anions generated by xanthine oxidase/hypoxanthine enhanced the contraction in the aortae with intact endothelium from sham rats, but had no effect in 2K1C rats. Enhanced contractile responses to norepinephrine by xanthine oxidase/hypoxanthine in sham rats were reversed by vitamin C.
These results suggest that the effect on endothelial modulation of endothelium-derived nitric oxide is impaired in 2K1C hypertension. The impairment is, at least in part, related to increased production of superoxide anions by NADH/NADPH oxidase.
内皮功能障碍与超氧阴离子的过度产生有关。本研究旨在探讨氧化应激对慢性双肾一夹（2K1C）肾高血压大鼠内皮调节收缩的影响。
通过夹闭左肾动脉诱导 2K1C 高血压；接受假手术治疗的年龄匹配大鼠作为对照。分离胸主动脉并置于组织浴中测量等长张力。
去内皮后，内皮源性一氧化氮产生抑制剂 Nω-硝基-L-精氨酸甲酯（Nω-硝基-L-精氨酸甲酯）增强了去甲肾上腺素诱导的收缩，在假手术大鼠中比在 2K1C 大鼠中更为明显。维生素 C 抑制了完整内皮的主动脉环中来自 2K1C 大鼠的收缩，但不抑制来自假手术大鼠的收缩。完整内皮的主动脉中，二苯乙烯碘化物或 apocynin（NADH/NADPH 氧化酶抑制剂）处理也抑制了收缩，但在来自假手术大鼠的主动脉中没有抑制。黄嘌呤氧化酶/次黄嘌呤产生的超氧阴离子增强了完整内皮的主动脉环中来自假手术大鼠的收缩，但对 2K1C 大鼠没有影响。黄嘌呤氧化酶/次黄嘌呤增强了来自假手术大鼠的去甲肾上腺素的收缩反应，被维生素 C 逆转。
这些结果表明，内皮衍生的一氧化氮对内皮调节的作用在 2K1C 高血压中受损。这种损伤至少部分与 NADH/NADPH 氧化酶产生的超氧阴离子增加有关。
