Neurovascular cognitive alterations: implication of brain renin-angiotensin system (RAS), therapeutic opportunities and risk factors

MARCHESE, N.A.; CASARSA, B.S.; BAIARDI, G.; BREGONZIO, C

Psychiatry and Neuroscience Update

Springer International

Año: 2015; p. 101 - 117

The neurovascular unit which comprises the microenvironmentwithin small blood vessels in the brain parenchyma is responsible forthe maintenance of normal neuronal function by a continuous supplyof nutrients. Inflammatory processes and loss of brain?blood-barrier(BBB) integrity can lead to vascular dysfunction and pathologicalinteractions between microvasculature, neurons, and astrocytes.These events have been closely related to the development of braindisorders such as cognitive decline, supported by numerous studiesusing hypertension animal models. There is a large body of evidenceshowing the implication of circulating and local renin angiotensinsystem in cerebral microvasculature function. Angiotensin II, troughAT 1 receptor activation, has been related to elevated reactive oxygenspecies production, endothelial dysfunction, elevated permeability,inflammatory events, and vascular structure alterations. Theangiotensin receptor blockers, used in antihypertensive treatments,are an important pharmacologic tool with neuroprotective effectsbecause they can modify vascular damage and improve cognitivealterations. The development of vascular diseases can be influencedand promoted by external factors such as stress and drug abuse. Stressis related to induction of structural changes in arteries and cytokineproduction leading to endothelial damage and inflammation. It isknown that psychostimulants have cardiovascular stimulant effectsthat can promote cerebral vasculitis and intracranial hemorrhage bydirect and indirect mechanisms on the vasculature. The brain renin?angiotensin system is becoming an interesting new therapeutic targetfor vascular and related cognitive disorders.