Hypertension accelerates age-related intrarenal small artery (IRSA) remodelling and stiffness in rats with possible involvement of AGEs and RAGE.
2020
Objectives. To study changes in morphology,
advanced glycation end products (AGEs) and the AGEs
receptor, RAGE, that occur with ageing in intrarenal
small arteries (IRSAs) of spontaneously hypertensive
rats (SHRs) and to investigate the possible roles of
hypertension, AGEs and RAGE in the progression of
IRSA remodelling and stiffness with ageing in rats.
METHODS: Ageing SHRs and ageing normotensive
Wistar Kyoto (WKY) rats were studied. The minimal
renal vascular resistance (minRVR) was measured.
Renal arcuate arteries (RAAs) and interlobular arteries
(RILAs), the expression of α-smooth muscle actin,
proliferating cell nuclear antigen, AGEs, RAGE and the
plasma concentrations of AGEs were also examined.
RESULTS: The IRSA minRVR, wall thickening, cell
proliferation and collagen deposition in RILAs and
RAAs gradually increased with age in SHRs and were
much higher in 24-week-old SHRs than in age-matched
WKY rats (p<0.05); these indexes in WKY rats were
only elevated in the 72-week group (p<0.05). The
expression of RAGE in the RAA and RILA tunica media
in SHRs was upregulated by 24 weeks and 12 weeks
(p<0.05), respectively, while AGEs levels in the plasma
and in the IRSA tunica media were increased by 48
weeks (p<0.05) and increased gradually with age. The
levels of both RAGE and AGEs in WKY rats were
increased only at 72 weeks (p<0.05). CONCLUSION:
Hypertension accelerates the development of age-related
IRSA remodelling and stiffness in rats, which may be
related to upregulation of RAGE in the IRSA tunica
media and increased expression of AGEs at the late
stage.
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