Long-term systemic angiotensin II type 1 receptor blockade regulates mRNA expression of dorsomedial medulla renin-angiotensin system components
Long-term systemic angiotensin II type 1 receptor blockade regulates mRNA expression of dorsomedial medulla renin-angiotensin system components
复制标题
DOI：
10.1152/physiolgenomics.00167.2010
复制
发表时间：
2011-07-01
影响因子：
4.6
通讯作者：
Diz, Debra I.
中科院分区：
文献类型：
--
作者：
Gilliam-Davis, Shea;Gallagher, Patricia E.;Diz, Debra I.
在Fischer 344 （F344）大鼠中，用血管紧张素II型1 （AT(1)）受体阻滞剂L-158,809阻断肾素-血管紧张素系统（RAS） 1年，可防止与年龄相关的代谢功能损伤，类似于低胶质血管紧张素原（Aogen）转基因大鼠。脑RAS调节可能有助于长期系统性AT1拮抗剂的益处。我们评估了F344大鼠在3岁（年轻，n = 8）或15月龄（年老，n = 7）时以及在3 -15月龄的大鼠中使用20mg /l的AT1受体拮抗剂l -158,809（年老+ l， n = 6）的后内侧髓质中RAS成分的mRNA。与老年组相比，年轻组的Aogen和renin mRNA较低。老年组和老年+ L组血管紧张素转换酶（ACE） mRNA较年轻组低。与年轻或老年大鼠相比，老年+ L大鼠的ACE2和neprilysin表达明显升高。AT（1b）、AT(2)和Mas受体mRNA随治疗升高。老龄大鼠瘦素受体mRNA较低，L-158,809治疗可防止这种情况。双特异性磷酸酶1 (DUSP1) mRNA在Old + L组最高。综合相关求和显示Mas受体mRNA与食物摄入量呈正相关。研究结果为衰老过程中肾素和Aogen mRNA的调控提供了依据。长期阻断AT1受体可增加ACE2、neprilysin酶和MAS受体的mRNA，这可能会将ANG II的平衡转移到ANG-(1-7)，并防止瘦素受体及其信号通路的年龄相关性下降。
In Fischer 344 (F344) rats, renin-angiotensin system (RAS) blockade for 1 yr with the angiotensin II type 1 (AT(1)) receptor blocker L-158,809 prevents age-related impairments in metabolic function, similar to transgenic rats with low glial angiotensinogen (Aogen). Brain RAS regulation may contribute to the benefits of long-term systemic AT1 antagonism. We assessed the mRNA of RAS components in the dorsomedial medulla of F344 rats at 3 (young; n = 8) or 15 mo of age (old; n = 7) and in rats treated from 3 to 15 mo of age with 20 mg/l of the AT1 receptor antagonist L-158,809 (Old + L; n = 6). Aogen and renin mRNA were lower in the young compared with old group. Angiotensin-converting enzyme (ACE) mRNA was lower in the old and Old + L compared with the young group. ACE2 and neprilysin expression were significantly higher in Old + L compared with young or old rats. AT(1b), AT(2), and Mas receptor mRNA were higher with treatment. Leptin receptor mRNA was lower in the old rats and this was prevented by L-158,809 treatment. Dual-specificity phosphatase 1 (DUSP1) mRNA was highest in the Old + L group. Aggregate correlate summation revealed a positive relationship for Mas receptor mRNA with food intake. The findings provide evidence for regulation of dorsomedial medullary renin and Aogen mRNA during aging. Long-term AT1 receptor blockade increases the mRNA of the enzymes ACE2 and neprilysin and the MAS receptor, which could potentially shift the balance from ANG II to ANG-(1-7)and prevent age-related declines in the leptin receptor and its signaling pathway.