Neurovascular Cognitive Alterations: Implication of Brain Renin?Angiotensin System. Therapeutic Opportunities and Risk Factors

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

Psychiatry and Neuroscience Update Bridging the Divide

Springer

Año: 2015; p. 101 - 119

The neurovascular unit, that comprises the small blood vessel within the brain parenchyma, is responsible for the maintenance of normal neuronal function by a continuous nutrients supply. Inflammatory processes and loss of brain-blood-barrier integrity can lead to vascular dysfunction and pathological interactions between microvasculature, neurons and astrocytes. These events have been closely related with the development of brain disorders such as cognitive decline, supported by numerous studies using hypertension animal models. There is a large body of evidences showing the implication of circulating and local RAS in cerebral microvasculature function. Angiotensin II, trough AT1 receptor activation, has been related to elevated ROS production, endothelial dysfunction, elevated permeability, inflammatory events and vascular structure alterations. The angiotensin receptors blockers, used in antihypertensive treatments, are an important pharmacologic tool with neuroprotective effects, as they can modify vascular damage and improve cognitive alterations. The development of vascular diseases can be influenced and promoted by external factors such as stress and drug abuse. Stress is related with induction of structural changes in arteries and cytokines production leading to endothelial damage and inflammation. Psychostimulants have known cardiovascular stimulant effects that can promote cerebral vasculitis and intracranial hemorrhage, by direct and indirect mechanisms on the vasculature. Brain RAS is becoming an interesting new therapeutic target for vascular and related cognitive disorders.