ACTIVATION OF ENDOTHELIAL L-ARGININE PATHWAY IN RESISTANCE ARTERIES - EFFECT OF AGE AND HYPERTENSION
ACTIVATION OF ENDOTHELIAL L-ARGININE PATHWAY IN RESISTANCE ARTERIES - EFFECT OF AGE AND HYPERTENSION
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DOI：
10.1161/01.hyp.16.2.170
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发表时间：
1990-08-01
期刊：
影响因子：
8.3
通讯作者：
LUSCHER, TF
中科院分区：
文献类型：
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作者：
DOHI, Y;THIEL, MA;LUSCHER, TF
在导管动脉中，一氧化氮由血管内皮细胞中的L-精氨酸形成，并在乙酰胆碱刺激下释放。在8周龄和16~20周龄Wistar-京都大鼠和自发性高血压大鼠的肠系膜阻力动脉上，用视频尺寸分析仪研究了L-精氨酸通路的作用以及年龄和高血压对内皮依赖性血管调节的影响。去甲肾上腺素和苯肾上腺素引起收缩，这种收缩在去除内皮后类似地增强。一氧化氮形成的抑制剂NG-单甲基-L-精氨酸增强了收缩，但不如去除内皮。乙酰胆碱引起内皮依赖性松弛，腔内用药比腔外用药更明显。NG-单甲基-L-精氨酸、亚甲蓝和血红蛋白仅部分抑制该反应。随着年龄的增长，Wistar-京都大鼠对去甲肾上腺素反应的内皮依赖性抑制减少；在自发性高血压大鼠中，这种抑制比年龄匹配的Wistar-京都大鼠要小。在Wistar-京都大鼠中，腔内激活和腔外激活之间的差异在成年大鼠中变得更加明显。与Wistar-京都大鼠相比，成年自发性高血压大鼠对腔内乙酰胆碱的反应降低，但对腔外乙酰胆碱的反应不降低。因此，在大鼠肠系膜阻力动脉，基础状态下和乙酰胆碱刺激后，L-精氨酸释放一氧化氮，但仅部分参与内皮依赖性反应。随着年龄的增长和高血压，血管内皮细胞对去甲肾上腺素引起的收缩的抑制作用减弱。在高血压患者，血管内而不是腔外对内皮衍生的松弛因子的释放的激活是受损的。
In conduit arteries, nitric oxide is formed from L-arginine in the endothelium and released after stimulation with acetylcholine. The contribution of the L-arginine pathway and the effects of age and hypertension on endothelium-dependent vascular regulation were studied, using a video dimension analyzer, in pressurized and perfused mesenteric resistance arteries of 8- and 16-20-week-old Wistar-Kyoto and spontaneously hypertensive rats. Norepinephrine and phenylephrine caused contractions, which were similarly augmented after removal of the endothelium. NG-Monomethyl-L-arginine, an inhibitor of nitric oxide formation, augmented the contraction, but less than endothelial removal. Acetylcholine caused endothelium-dependent relaxations that were much more pronounced with intraluminal than with extraluminal application. NG-Monomethyl-L-arginine, methylene blue, and hemoglobin only partially inhibited the response. With aging, the endothelium-dependent inhibition of the response to norepinephrine decreased in Wistar-Kyoto rats; in spontaneously hypertensive rats this inhibition was smaller as compared with age-matched Wistar-Kyoto rats. In Wistar-Kyoto rats, the difference between intraluminal and extraluminal activation became more pronounced in adult rats. In the adult but not the young spontaneously hypertensive rats, the response to intraluminal but not extraluminal acetylcholine was reduced as compared with Wistar-Kyoto rats. Thus, in mesenteric resistance arteries of the rat, nitric oxide is released from L-arginine under basal conditions and after stimulation with acetylcholine but only in part accounts for endothelium-dependent responses. With aging and hypertension, the inhibitory effects of the endothelium against norepinephrine-induced contractions decrease. In hypertension, the intraluminal but not extraluminal activation of the release of endothelium-derived relaxing factors is impaired.