TY - JOUR
T1 - Neuroprotective effects of angiotensin receptor blockers
AU - Villapol, Sonia
AU - Saavedra, Juan M.
N1 - Funding Information:
SV is supported by the Partners in Research Program, Georgetown University Medical Center (GX4002705) and by the Department of Neurosciences, Georgetown University Medical Center. JMS is supported by the Partners in Research Program, Georgetown University Medical Center (GX4002705) and by the Department of Pharmacology and Physiology, Georgetown University Medical Center.
Publisher Copyright:
© American Journal of Hypertension, Ltd 2014. All rights reserved.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Angiotensin II
KW - Angiotensin receptor blockers
KW - Blood pressure
KW - Brain inflammation
KW - Hypertension
KW - Neurodegenerative disorders
KW - Neuronal injury
KW - Neuroprotection
KW - Parkinson's disease
KW - Renin-angiotensin system
KW - Sartans
KW - Traumatic brain injury
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U2 - 10.1093/ajh/hpu197
DO - 10.1093/ajh/hpu197
M3 - Review article
C2 - 25362113
AN - SCOPUS:84935110912
SN - 0895-7061
VL - 28
SP - 289
EP - 299
JO - American Journal of Hypertension
JF - American Journal of Hypertension
IS - 3
ER -