Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32610, USA.
Circ Res. 2010 Oct 1;107(7):934-8. doi: 10.1161/CIRCRESAHA.110.226977. Epub 2010 Aug 5.
Despite overwhelming evidence of the importance of brain renin-angiotensin system (RAS), the very existence of intrinsic brain RAS remains controversial.
To investigate the hypothesis that the brain (pro)renin receptor (PRR) is physiologically important in the brain RAS regulation and cardiovascular functions.
PRR is broadly distributed within neurons of cardiovascular-relevant brain regions. The physiological functions of PRR were studied in the supraoptic nucleus (SON) because this brain region showed greater levels of PRR mRNA in the spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto (WKY) rats. Adeno-associated virus (AAV)-mediated overexpression of human PRR in the SON of normal rats resulted in increases in plasma and urine vasopressin, and decreases in H(2)O intake and urine output without any effects on mean arterial pressure and heart rate. Knockdown of endogenous PRR by AAV-short hairpin RNA in the SON of SHRs attenuated age-dependent increases in mean arterial pressure and caused a decrease in heart rate and plasma vasopressin. Incubation of neuronal cells in culture with human prorenin and angiotensinogen resulted in increased generation of angiotensin I and II. Furthermore, renin treatment increased phosphorylation of extracellular signal-regulated kinase ½ in neurons from both WKY rats and SHRs; however, the stimulation was 50% greater in the SHR.
The study demonstrates that brain PRR is functional and plays a role in the neural control of cardiovascular functions. This may help resolve a long-held controversy concerning the existence of intrinsic and functional brain RAS.
尽管有大量证据表明脑肾素-血管紧张素系统（RAS）的重要性，但内源性脑 RAS 的存在仍然存在争议。
研究假设脑（前）肾素受体（PRR）在脑 RAS 调节和心血管功能中具有重要的生理作用。
PRR 在心血管相关脑区的神经元中广泛分布。PRR 的生理功能在视上核（SON）中进行了研究，因为与正常血压的 Wistar-Kyoto（WKY）大鼠相比，该脑区的 PRR mRNA 水平更高。在正常大鼠的 SON 中，腺相关病毒（AAV）介导的人 PRR 的过表达导致血浆和尿液血管升压素增加，H2O 摄入和尿液排泄减少，而对平均动脉压和心率没有任何影响。在 SHR 的 SON 中，AAV-short hairpin RNA 下调内源性 PRR 可减弱年龄依赖性的平均动脉压升高，并导致心率和血浆血管升压素降低。在培养的神经元细胞中，与人前肾素和血管紧张素原孵育可导致血管紧张素 I 和 II 的生成增加。此外，肾素处理可增加 WKY 大鼠和 SHR 神经元中细胞外信号调节激酶 1/2 的磷酸化；然而，在 SHR 中刺激增加了 50%。
该研究表明，脑 PRR 具有功能，在心血管功能的神经控制中起作用。这可能有助于解决长期以来关于内源性和功能性脑 RAS 存在的争议。
