Departamento de Fisiologia e Farmacologia, Universidade Federal de Pernambuco, Recife, Brazil.
Departamento de Fisiologia e Farmacologia, Universidade Federal de Pernambuco, Recife, Brazil.
Vascul Pharmacol. 2019 Apr;115:33-45. doi: 10.1016/j.vph.2019.02.001. Epub 2019 Feb 18.
Perinatal sodium overload induces endothelial dysfunction in adult offspring, but the underlying mechanisms are not fully known. The involvement of tissue renin-angiotensin system on high sodium-programmed endothelial dysfunction was examined. Acetylcholine and angiotensin I and II responses were analyzed in aorta and mesenteric resistance arteries from 24-week-old male offspring of normal-salt (O-NS, 1.3% NaCl) and high-salt (O-HS, 8% NaCl) fed dams. COX-2 expression, O production and angiotensin converting enzyme (ACE) activity were determined. A separated O-HS was treated with losartan (15 mg kg/day) for eight weeks. Compared to O-NS, O-HS were normotensive. Acetylcholine-induced relaxation was impaired in O-HS arteries, which was improved by tempol, apocynin or indomethacin. The angiotensin I-induced contraction was greater in O-HS arteries, whereas the angiotensin II responses were unchanged. ACE activity, O production and COX-2 expression were increased in O-HS arteries. In this group, the increased O production was inhibited by apocynin or losartan. Chronic losartan decreased COX-2 expression and restored the endothelium-dependent vasodilation in O-HS. Our findings reiterate that perinatal sodium overload programs endothelial dysfunction in adult offspring through a blood pressure-independent mechanism. Our results also suggest that vascular angiotensin II is the main mediator of high sodium-programmed endothelial dysfunction, promoting COX-2 expression and oxidative stress.
围产期钠负荷导致成年子代内皮功能障碍，但具体机制尚不完全清楚。本研究旨在探讨组织肾素-血管紧张素系统（RAS）在高盐程序化内皮功能障碍中的作用。检测了正常盐（O-NS，1.3%NaCl）和高盐（O-HS，8%NaCl）饮食组孕鼠所生 24 周龄雄性子代主动脉和肠系膜阻力血管对乙酰胆碱和血管紧张素 I、II 的反应。测定了 COX-2 表达、O 生成和血管紧张素转换酶（ACE）活性。将单独的 O-HS 用氯沙坦（15mg/kg/天）处理 8 周。与 O-NS 相比，O-HS 血压正常。与 O-NS 相比，O-HS 组乙酰胆碱诱导的血管舒张功能受损，该作用可被 tempol、apocynin 或吲哚美辛改善。O-HS 组血管对血管紧张素 I 的收缩反应增强，而对血管紧张素 II 的反应无变化。O-HS 组的 ACE 活性、O 生成和 COX-2 表达增加。在该组中，apocynin 或氯沙坦抑制 O 生成增加。慢性氯沙坦降低了 COX-2 表达，恢复了 O-HS 内皮依赖性血管舒张。我们的研究结果再次表明，围产期钠负荷通过一种血压非依赖性机制导致成年子代内皮功能障碍。我们的结果还表明，血管紧张素 II 是高盐程序化内皮功能障碍的主要介质，促进 COX-2 表达和氧化应激。
