L-精氨酸酶可诱导老年自发性高血压大鼠出现血管功能障碍。
L-arginase induces vascular dysfunction in old spontaneously hypertensive rats.
作者信息
Arishe O, McKenzie J, Priviero F, Ebeigbe A B, Webb R Clinton
机构信息
Department of Physiology, Medical College of Georgia at Augusta University, Augusta, GA, USA.
Department of Physiology College of Medical Sciences, University of Benin, Benin City, Nigeria.
出版信息
J Afr Assoc Physiol Sci. 2019 Dec;7(2):119-127.
BACKGROUND
Aging is a major non-modifiable risk factor for hypertension. Changes in aging are similar to those seen in hypertension in the vasculature. Also, aging increases the vascular dysfunction that occurs in hypertension. L-arginase action reduces substrate (L-arginine) availability for the formation of nitric oxide (NO). This reduces the level of NO and leads to reduced vasodilation and ultimately, vascular dysfunction. This study examines the hypothesis that age-dependent vascular dysfunction in SHRs is mediated by arginase.
METHODS
Young (12-14 weeks) and old (11-12 months) male Wistar and spontaneously hypertensive rats (SHR) were used. Mean arterial pressure (MAP) was measured in the rats. They were then euthanized and mesenteric resistance arteries (MRAs) and thoracic aortae were excised and placed in ice-cold physiological salt solution (PSS). Arterial segments were either snap-frozen in liquid nitrogen and stored for immunoblotting studies or cut into 2mm rings for reactivity studies. Cumulative concentration-response curves to acetylcholine (Ach: 10 - 3x10M) and sodium nitroprusside (SNP: 10 - 3x10 M) were performed in the absence or presence (30-minute exposure) of L-arginase, 0.05U/ML (MRA) or 0.5U/ML (aorta). Vessels were pre-contracted with phenylephrine (PE; 3x10M).
RESULTS
MAP increased during aging in the SHRs p<0.05 but not in the Wistar rats. Arginase impaired the endothelium-dependent relaxation responses of thoracic aortic and MRA arterial rings to Ach in the old Wistars and SHRs (Emax aorta: 29.42±2.19% vs 7.94±1.86%). Arginase also impaired endothelium-independent relaxation response to SNP in the old SHRs only (Emax aorta: 88.62±4.10% vs 31.45±10.61%). We also observed no differences in the serum arginase activity in the four groups of rats. On the contrary, arginase activity in the aortae of young Wistar rats was reduced compared to other groups.
CONCLUSIONS
Arginase impairs both endothelium-dependent and -independent vasorelaxation responses, through the NO signaling pathway.
背景
衰老是非可改变的高血压主要危险因素。衰老过程中的变化与高血压时血管系统的变化相似。此外，衰老会加剧高血压时出现的血管功能障碍。L-精氨酸酶的作用会减少一氧化氮（NO）形成所需底物（L-精氨酸）的可用性。这会降低NO水平，导致血管舒张减少，最终引发血管功能障碍。本研究检验了以下假设：自发性高血压大鼠（SHR）中与年龄相关的血管功能障碍是由精氨酸酶介导的。
方法
使用年轻（12 - 14周）和年老（11 - 12个月）的雄性Wistar大鼠和自发性高血压大鼠（SHR）。测量大鼠的平均动脉压（MAP）。然后对其实施安乐死，切除肠系膜阻力动脉（MRA）和胸主动脉，并置于冰冷的生理盐溶液（PSS）中。动脉段要么在液氮中速冻并储存用于免疫印迹研究，要么切成2毫米的环用于反应性研究。在不存在或存在（暴露30分钟）L-精氨酸酶（0.05U/ML（MRA）或0.5U/ML（主动脉））的情况下，进行对乙酰胆碱（Ach：10 - 3×10M）和硝普钠（SNP：10 - 3×10M）的累积浓度 - 反应曲线实验。血管先用去氧肾上腺素（PE；3×10M）预收缩。
结果
SHR衰老过程中MAP升高（p<0.05），而Wistar大鼠未出现此情况。精氨酸酶损害了年老Wistar大鼠和SHR胸主动脉及MRA动脉环对Ach的内皮依赖性舒张反应（主动脉最大效应：29.42±2.19%对7.94±1.86%）。精氨酸酶还仅损害了年老SHR对SNP的非内皮依赖性舒张反应（主动脉最大效应：88.62±4.10%对31.45±10.61%）。我们还观察到四组大鼠血清精氨酸酶活性无差异。相反，年轻Wistar大鼠主动脉中的精氨酸酶活性与其他组相比降低。
结论
精氨酸酶通过NO信号通路损害内皮依赖性和非内皮依赖性血管舒张反应。
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