Differential expression of AT1 receptors in the pituitary and adrenal gland of SHR and WKY
Differential expression of AT1 receptors in the pituitary and adrenal gland of SHR and WKY
复制标题
DOI：
10.1161/01.hyp.0000062466.38314.b7
复制
发表时间：
2003-04-01
期刊：
影响因子：
8.3
通讯作者：
Dominiak, P
中科院分区：
文献类型：
--
作者：
Jöhren, O;Golsch, C;Dominiak, P
肾素-血管紧张素（ANG）系统与自发性高血压大鼠（SHR）高血压的发生有关。由于SHR比正常的Wistar-Kyoto大鼠（WKY）更容易受到应激的影响，我们测量了雄性SHR下丘脑-垂体-肾上腺（应激）轴AT（1A）、AT（1B）和AT(2)受体的mRNA表达，并将其与年龄匹配的WKY在高血压前期（3至4周）、发展中（7至8周）和确立期（12至13周）高血压阶段进行比较。AT（1A）受体mRNA主要表达于下丘脑和肾上腺。垂体和肾上腺中检测到AT（1B）受体mRNA。AT(2)受体mRNA仅在肾上腺中表达显著。与WKY相比，SHR在各年龄段均显示垂体AT（1A）受体mRNA水平升高，而垂体AT1B受体mRNA水平降低。在SHR的肾上腺中，与WKY相比，AT（1B）受体mRNA水平在高血压期降低。原位杂交表明，肾上腺AT（1B）受体mRNA的表达减少选择性地定位于肾小球带。WKY和SHR在下丘脑ANG受体表达上无差异。在地塞米松治疗的SHR中，ANG显著增加血浆促肾上腺皮质激素（ACTH）和皮质酮水平，但在WKY中没有。SHR和WKY对ANG的醛固酮反应相似。我们的研究结果表明，在SHR和正常WKY的下丘脑-垂体-肾上腺轴上，AT（1A）和AT（1B）受体的基因表达存在差异，并暗示AT(1)受体参与了SHR对ANG的过度内分泌应激反应。
The renin-angiotensin (ANG) system has been implicated in the development of hypertension in spontaneously hypertensive rats (SHR). Because SHR are more susceptible to stress than normotensive Wistar-Kyoto rats (WKY), we measured the mRNA expression of AT(1A), AT(1B), and AT(2) receptors in the hypothalamo-pituitary-adrenal (stress) axis of male SHR in comparison to age-matched WKY at prehypertensive (3 to 4 weeks), developing (7 to 8 weeks), and established (12 to 13 weeks) stages of hypertension. AT(1A) receptor mRNA was mainly expressed in the hypothalamus and adrenal gland. AT(1B) receptor mRNA was detected in the pituitary and adrenal gland. AT(2) receptor mRNA was prominent only in the adrenal gland. When compared with WKY, SHR showed increased AT(1A) receptor mRNA levels in the pituitary gland at all ages in contrast to reduced pituitary AT1B receptor mRNA levels. In the adrenal gland of SHR, AT(1B) receptor mRNA levels were decreased at the hypertensive stages when compared with WKY. The reduced expression of adrenal AT(1B) receptor mRNA was localized selectively in the zona glomerulosa by in situ hybridization. No differences were observed between WKY and SHR in the expression of hypothalamic ANG receptors. ANG significantly increased plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone in dexamethasone-treated SHR but not in WKY. The aldosterone response to ANG was similar in SHR and WKY. Our results suggest a differential gene expression of AT(1A) and AT(1B) receptors in the hypothalamo-pituitary-adrenal axis of SHR and normotensive WKY and imply the participation of AT(1) receptors in an exaggerated endocrine stress response of SHR to ANG.