BLOOD-BRAIN BARRIER AND AUTONOMIC REGULATION IN HYPERTENSION: EFFECTS OF ANGIOTENSIN II AND AEROBIC TRAINING

Abstract

Arterial hypertension (AH) is a chronic disease of high incidence that is accompanied by sympathetic hyperactivity and important imbalance of the autonomic circulatory control. Recent studies in hypertensive animals suggested that deleterious changes in brain perfusion, specifically in the blood-brain barrier (BBB) function, could contribute to the autonomic dysfunction and sympathetic hyperactivity. The mechanisms by which hypertension affects BBB structure/activity are not completely understood. A recent observation has suggested that hyperactivity of the renin-angiotensin system (RAS, and specifically that of Angiotensin II, via AT1 receptors) in spontaneously hypertensive (SHR) and renal hypertensive rats, by acting on autonomic areas, compromise the integrity of BBB, but there is no information on which BBB component is affected by the development of hypertension. On the other hand studies from our and other laboratories have shown that aerobic training is an efficient tool to reduce the expression/activity of brain RAS and to simultaneously correct autonomic dysfunction. It is our hypothesis that RAS hyperactivity, already shown in hypertensive animals, could be an important factor to cause BBB leakage and that aerobic training, by reducing brain RAS activity, could improve the integrity of the BBB, therefore facilitating the autonomic control of the circulation. The present study aims to investigate: 1) the presence of BBB lesion, the structural alterations in its components and the possible correlation with autonomic dysfunction in autonomic brain areas (paraventricular hypothalamic nucleus, nucleus of the solitary tract and rostroventrolateral medulla) of SHR; 2) the effects of aerobic training to reduce/correct the deleterious effects of AH on BBB and autonomic dysfunction; 3) the effects of exogenous administration of Ang II and of its endogenous blockade on the lesion and/or integrity of the BBB in SHR and respective controls submitted to training or sedentary protocols. Together these results will allow us to identify the mechanisms conditioning the effects of AH associated or not with aerobic training, on the structure and function of BBB. Importantly, these studies will uncover the role of BBB function for an adequate perfusion of the central nervous system, the consequences determined by hypertension, besides giving clues on appropriate therapeutic tools to improve/reverse their deleterious effects on cardiovascular control. (AU)