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衰老正常血压和自发性高血压大鼠的肾上腺 α2-肾上腺素能受体。

Adrenal α2-adrenergic receptors in the aging normotensive and spontaneously hypertensive rat.

机构信息

Institute of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.

出版信息

Neurobiol Aging. 2012 May;33(5):969-78. doi: 10.1016/j.neurobiolaging.2010.06.021. Epub 2010 Aug 5.

Abstract

This study investigates α(2)-adrenergic receptor (α(2)AR) mediated feedback inhibition of catecholamine release from the adrenal medulla of adult (52 weeks) and old (98 weeks) spontaneously hypertensive rats (SHR) and normotensive controls Wistar Kyoto (WKY) rats. Adrenal epinephrine content as well as the spontaneous and the nicotinic-evoked release of epinephrine were similar between adult SHR and WKY rats. Aging produced a significant reduction in epinephrine synthesis in WKY rats. In contrast, in SHR aging produced a significant increase in epinephrine release without significant changes in epinephrine synthesis. The α(2)AR agonist medetomidine abolished (80-90% inhibition) the nicotinic-evoked release of epinephrine in adult SHR and WKY rats. With aging, this effect was unaltered in WKY rats but was significantly decreased in SHR (30% inhibition). Adrenal α(2A)AR mRNA levels were significantly reduced in old SHR compared with age matched WKY rats. In conclusion, in aging the α(2)AR mediated feedback inhibition of epinephrine release from the adrenal medulla is preserved in WKY rats but compromised in SHR, resulting in increased epinephrine release.

摘要

本研究探讨了α(2)-肾上腺素能受体(α(2)AR)对成年(52 周)和老年(98 周)自发性高血压大鼠(SHR)和正常血压对照 Wistar Kyoto(WKY)大鼠肾上腺髓质儿茶酚胺释放的反馈抑制作用。成年 SHR 和 WKY 大鼠的肾上腺肾上腺素含量以及自发性和烟碱诱发的肾上腺素释放相似。衰老导致 WKY 大鼠肾上腺素合成显著减少。相比之下,衰老在 SHR 中产生了显著增加的肾上腺素释放,而肾上腺素合成没有明显变化。α(2)AR 激动剂美托咪定可消除(80-90%的抑制作用)成年 SHR 和 WKY 大鼠的烟碱诱发的肾上腺素释放。随着衰老,这种作用在 WKY 大鼠中没有改变,但在 SHR 中显著降低(30%的抑制作用)。与年龄匹配的 WKY 大鼠相比,老年 SHR 的肾上腺 α(2A)AR mRNA 水平显著降低。总之,在衰老过程中,WKY 大鼠的肾上腺髓质肾上腺素释放的 α(2)AR 介导的反馈抑制作用得以保留,但 SHR 受损,导致肾上腺素释放增加。

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