Davidson Eric P, Coppey Lawrence J, Dake Brian, Yorek Mark A
Veteran Affairs Medical Center, Iowa City, IA 52246, USA.
J Obes. 2011;2011. doi: 10.1155/2011/686952. Epub 2010 Aug 16.
The objective of this study was to determine the effect of AVE7688, a drug that inhibits both angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) activity, on neural and vascular defects caused by diet induced obesity (DIO). Rats at 12 weeks of age were fed a standard or high fat diet with or without AVE7688 for 24 weeks. DIO rats had impaired glucose tolerance and developed sensory neuropathy. Vascular relaxation to acetylcholine and calcitonin gene-related peptide was decreased in epineurial arterioles of DIO rats. Rats fed a high fat diet containing AVE7688 did not become obese and vascular and sensory nerve dysfunction and impaired glucose tolerance were improved. DIO is associated with increased expression of NEP in epineurial arterioles. NEP degrades vasoactive peptides which may explain the decrease in neurovascular function in DIO.
本研究的目的是确定一种同时抑制血管紧张素转换酶（ACE）和中性内肽酶（NEP）活性的药物AVE7688对饮食诱导肥胖（DIO）所致神经和血管缺陷的影响。12周龄的大鼠被喂食标准或高脂肪饮食，同时给予或不给予AVE7688，持续24周。DIO大鼠糖耐量受损并出现感觉神经病变。DIO大鼠的神经外膜小动脉对乙酰胆碱和降钙素基因相关肽的血管舒张反应降低。喂食含AVE7688高脂肪饮食的大鼠未出现肥胖，血管和感觉神经功能障碍以及糖耐量受损均得到改善。DIO与神经外膜小动脉中NEP表达增加有关。NEP可降解血管活性肽，这可能解释了DIO中神经血管功能下降的原因。
