Departamento de Ciencias Médicas Básicas, Facultad de Ciencias de la Salud, Campus de Ofra, Universidad de La Laguna (ULL), 38200 Santa Cruz de Tenerife, Spain.
Instituto Universitario de Neurociencia (IUNE), Campus de Guajara, Universidad de La Laguna, 38205 Santa Cruz de Tenerife, Spain.
Int J Mol Sci. 2022 Oct 14;23(20):12277. doi: 10.3390/ijms232012277.
Hypertension is the leading cause of cardiovascular affection and premature death worldwide. The spontaneously hypertensive rat (SHR) is the most common animal model of hypertension, which is characterized by secondary ventricular dilation and hydrocephalus. Aquaporin (AQP) 1 and 4 are the main water channels responsible for the brain’s water balance. The present study focuses on defining the expression of AQPs through the time course of the development of spontaneous chronic hypertension. We performed immunofluorescence and ELISA to examine brain AQPs from 10 SHR, and 10 Wistar−Kyoto (WKY) rats studied at 6 and 12 months old. There was a significant decrease in AQP1 in the choroid plexus of the SHR-12-months group compared with the age-matched control (p < 0.05). In the ependyma, AQP4 was significantly decreased only in the SHR-12-months group compared with the control or SHR-6-months groups (p < 0.05). Per contra, AQP4 increased in astrocytes end-feet of 6 months and 12 months SHR rats (p < 0.05). CSF AQP detection was higher in the SHR-12-months group than in the age-matched control group. CSF findings were confirmed by Western blot. In SHR, ependymal and choroidal AQPs decreased over time, while CSF AQPs levels increased. In turn, astrocytes AQP4 increased in SHR rats. These AQP alterations may underlie hypertensive-dependent ventriculomegaly.
高血压是全球心血管疾病和过早死亡的主要原因。自发性高血压大鼠(SHR)是高血压最常见的动物模型,其特征是继发性心室扩张和脑积水。水通道蛋白(AQP)1 和 4 是负责大脑水平衡的主要水通道。本研究旨在通过自发性慢性高血压发展的时间过程来定义 AQP 的表达。我们使用免疫荧光和 ELISA 检查了 10 只 SHR 和 10 只 Wistar-Kyoto(WKY)大鼠在 6 个月和 12 个月时的大脑 AQP。与年龄匹配的对照组相比,SHR-12 个月组的脉络丛 AQP1 显著减少(p<0.05)。在室管膜中,仅在 SHR-12 个月组与对照组或 SHR-6 个月组相比,AQP4 显著减少(p<0.05)。相反,6 个月和 12 个月 SHR 大鼠的星形胶质细胞终足中 AQP4 增加(p<0.05)。CSF AQP 的检测在 SHR-12 个月组中高于年龄匹配的对照组。CSF 发现得到了 Western blot 的证实。在 SHR 中,随着时间的推移,室管膜和脉络丛 AQP 减少,而 CSF AQP 水平增加。反过来,SHR 大鼠的星形胶质细胞 AQP4 增加。这些 AQP 改变可能是高血压依赖性脑室扩张的基础。