Altered Expression of AQP1 and AQP4 in Brain Barriers and Cerebrospinal Fluid May Affect Cerebral Water Balance during Chronic Hypertension

Int J Mol Sci. 2022 Oct 14;23(20):12277. doi: 10.3390/ijms232012277.

Abstract

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.

Keywords: SHR; aquaporins; cerebrospinal fluid; choroid plexus; ependyma; hydrocephalus; hypertension.

MeSH terms

  • Animals
  • Aquaporin 1 / metabolism
  • Aquaporin 4 / metabolism
  • Aquaporins* / metabolism
  • Brain / metabolism
  • Hydrocephalus* / metabolism
  • Hypertension* / metabolism
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Water / metabolism

Substances

  • Aquaporin 1
  • Water
  • Aquaporin 4
  • Aquaporins
  • Aqp1 protein, rat
  • Aqp4 protein, rat

Grants and funding

This work was supported by the University of La Laguna and the Canary Council of Economy, Knowledge, and Employment (CEI program) is acknowledged.