Strong reduction of low-density lipoprotein receptor/apolipoprotein e expressions by telmisartan in cerebral cortex and hippocampus of stroke resistant spontaneously hypertensive rats

Background: Telmisartan is a unique angiotensin II type 1 receptor blocker with a partial peroxisome proliferator-Activated receptorγ (PPARγ) agonistic property to exert not only antihypertensive effect but also antimetabolic syndrome effect.

Methods: We examined the long-term effect of telmisartan on cholesterol transport-related proteins (low-density lipoprotein receptor [LDL-R]/apolipoprotein E [ApoE]) and microtubule-Associated proteins 2 (MAP2) in the brains of stroke resistant spontaneously hypertensive rats (SHR-SRs), which were divided into 3 experiment groups including vehicle group (SHR/Ve), low-dose telmisartan group (SHR/Low, .3 mg/kg/day), and high-dose telmisartan group (SHR/High, 3 mg/kg/day).

Results: The numbers of LDL-R and immuno-ApoEpositive neurons increased in both cerebral cortex and hippocampus of SHR/Ve throughout 6, 12, and 18 months of age, compared with age-matched normotensiveWistar rats. On the other hand, telmisartan significantly reduced the numbers of LDL-R and ApoE immuno-positive neurons in both cerebral cortex and hippocampus, with similar effectiveness in the SHR/Low group without blood pressure (BP) lowering to BP lowering (SHR/High). The decrease of MAP2-positive neuron in SHR/Ve was recovered by telmisartan in both cerebral cortex and hippocampus.

Conclusions: These findings suggest that a long-term treatment with telmisartan directly improved neuronal lipid metabolism in the cerebral cortex and hippocampus of SHR-SR, mainly improving LDL-R and ApoE metabolism (SHR/Low) with a small additive benefit by BP lowering (SHR/High), which could provide a preventative approach in patients with hypertension at risk of Alzheimer disease.