Neuroprotective effects of angiotensin receptor blockers

Sonia Villapol, Juan M. Saavedra

    Research output: Contribution to journalReview articlepeer-review

    155 Scopus citations

    Abstract

    Angiotensin II receptor blockers (ARBs, collectively called sartans) are widely used compounds therapeutically effective in cardiovascular disorders, renal disease, the metabolic syndrome, and diabetes. It has been more recently recognized that ARBs are neuroprotective and have potential therapeutic use in many brain disorders. ARBs ameliorate inflammatory and apoptotic responses to glutamate, interleukin 1β and bacterial endotoxin in cultured neurons, astrocytes, microglial, and endothelial cerebrovascular cells. When administered systemically, ARBs enter the brain, protecting cerebral blood flow, maintaining blood brain barrier function and decreasing cerebral hemorrhage, excessive brain inflammation and neuronal injury in animal models of stroke, traumatic brain injury, Alzheimer's and Parkinson's disease and other brain conditions. Epidemiological analyses reported that ARBs reduced the progression of Alzheimer's disease, and clinical studies suggested amelioration of cognitive loss following stroke and aging. ARBs are pharmacologically heterogeneous; their effects are not only the result of Ang II type 1(AT1) receptor blockade but also of additional mechanisms selective for only some compounds of the class. These include peroxisome proliferator-activated receptor gamma activation and other still poorly defined mechanisms. However, the complete pharmacological spectrum and therapeutic efficacy of individual ARBs have never been systematically compared, and the neuroprotective efficacy of these compounds has not been rigorously determined in controlled clinical studies. The accumulation of pre-clinical evidence should promote further epidemiological and controlled clinical studies. Repurposing ARBs for the treatment of brain disorders, currently without effective therapy, may be of immediate and major translational value.

    Original languageEnglish (US)
    Pages (from-to)289-299
    Number of pages11
    JournalAmerican Journal of Hypertension
    Volume28
    Issue number3
    DOIs
    StatePublished - 2015

    Keywords

    • Alzheimer's disease
    • Angiotensin II
    • Angiotensin receptor blockers
    • Blood pressure
    • Brain inflammation
    • Hypertension
    • Neurodegenerative disorders
    • Neuronal injury
    • Neuroprotection
    • Parkinson's disease
    • Renin-angiotensin system
    • Sartans
    • Traumatic brain injury

    ASJC Scopus subject areas

    • Internal Medicine

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