Allen Andrew M, Dosanjh Jaspreet K, Erac Marco, Dassanayake Sashikala, Hannan Ross D, Thomas Walter G
Department of Physiology, University of Melbourne, Victoria, Australia.
Hypertension. 2006 Jun;47(6):1054-61. doi: 10.1161/01.HYP.0000218576.36574.54. Epub 2006 Apr 17.
Angiotensin type 1A (AT(1A)) receptors are expressed within the rostral ventrolateral medulla, and microinjections of angiotensin II into this region increase sympathetic vasomotor tone. To determine the effect of sustained increases in AT(1A) receptor density or activity in rostral ventrolateral medulla, we used radiotelemetry to monitor blood pressure in conscious rats before and after bilateral microinjection into the rostral ventrolateral medulla of adenoviruses encoding the wild-type AT(1A) receptor or a constitutively active version of the receptor (Asn111Gly, [N111G]AT(1A)). The constitutively active receptor signals in the absence of angiotensin II. Adenovirus-directed receptor expression was extensively characterized both in vitro and in vivo. We established that adenoviral infection was limited to the rostral ventrolateral medulla and that receptor expression was sustained for > or =10 days; we also observed that adenoviral transgene expression occurs in glia, with no transgene expression observed in neurons of the rostral ventrolateral medulla. Rats receiving the wild-type AT(1A) receptor showed no change in blood pressure, whereas animals receiving the [N111G]AT(1A) receptor displayed an increase in blood pressure that persisted for 3 to 4 days before returning to basal levels. These data indicate that increased AT(1A) receptor activity (not just overexpression) is a primary determinant of efferent drive from rostral ventrolateral medulla and reveal counterregulatory processes that moderate AT(1A) receptor actions at this crucial relay point. More importantly, they imply that constitutive receptor signaling in glia of the rostral ventrolateral medulla can modulate the activity of adjacent neurons to change blood pressure.
1A型血管紧张素（AT(1A)）受体表达于延髓头端腹外侧区，向该区域微量注射血管紧张素II可增强交感缩血管紧张。为了确定延髓头端腹外侧区AT(1A)受体密度或活性持续增加的影响，我们在向延髓头端腹外侧区双侧微量注射编码野生型AT(1A)受体或该受体组成型活性形式（Asn111Gly，[N111G]AT(1A)）的腺病毒之前和之后，使用无线电遥测技术监测清醒大鼠的血压。组成型活性受体在无血管紧张素II的情况下发出信号。腺病毒介导的受体表达在体外和体内均得到了广泛表征。我们确定腺病毒感染仅限于延髓头端腹外侧区，并且受体表达持续≥10天；我们还观察到腺病毒转基因表达发生在胶质细胞中，而在延髓头端腹外侧区的神经元中未观察到转基因表达。接受野生型AT(1A)受体的大鼠血压无变化，而接受[N111G]AT(1A)受体的动物血压升高，持续3至4天，然后恢复到基础水平。这些数据表明，AT(1A)受体活性增加（不仅仅是过表达）是延髓头端腹外侧区传出驱动的主要决定因素，并揭示了在这个关键中继点调节AT(1A)受体作用的反调节过程。更重要的是，它们暗示延髓头端腹外侧区胶质细胞中的组成型受体信号传导可调节相邻神经元的活性以改变血压。
