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Blood-brain barrier and autonomic regulation in hypertension: effects of Angiotensin II and aerobic training

Grant number: 15/24935-4
Support type:Regular Research Grants
Duration: August 01, 2016 - July 31, 2018
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Lisete Compagno Michelini
Grantee:Lisete Compagno Michelini
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Nilson Carlos Ferreira Junior

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)

Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FERREIRA-JUNIOR, NILSON C.; RUGGERI, ADRIANA; SILVA JR, SEBASTIAO D.; ZAMPIERI, THAIS T.; CERONI, ALEXANDRE; MICHELINI, LISETE C. Exercise training increases GAD65 expression, restores the depressed GABA(A) receptor function within the PVN and reduces sympathetic modulation in hypertension. PHYSIOLOGICAL REPORTS, v. 7, n. 13 JUL 2019. Web of Science Citations: 0.
DAMPNEY, ROGER A.; MICHELINI, LISETE C.; LI, DE-PEI; PAN, HUI-LIN. Regulation of sympathetic vasomotor activity by the hypothalamic paraventricular nucleus in normotensive and hypertensive states. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, v. 315, n. 5, p. H1200-H1214, NOV 2018. Web of Science Citations: 8.
RAQUEL, HIVINY DE ATAIDES; FERREIRA, NATHALIA ZERBINATTI; CRUZ LUCCHETTI, BRUNO FERNANDO; FALQUETTO, BARBARA; PINGE-FILHO, PHILENO; MICHELINI, LISETE COMPAGNO; MARTINS-PINGE, MARLI CARDOSO. The essential role of hypothalamic paraventricular nucleus nNOS in the modulation of autonomic control in exercised rats. NITRIC OXIDE-BIOLOGY AND CHEMISTRY, v. 79, p. 14-24, SEP 1 2018. Web of Science Citations: 1.
SANTOS, C. R.; RUGGERI, A.; CERONI, A.; MICHELINI, L. C. Exercise training abrogates age-dependent loss of hypothalamic oxytocinergic circuitry and maintains high parasympathetic activity. Journal of Neuroendocrinology, v. 30, n. 8, SI AUG 2018. Web of Science Citations: 2.
BUTTLER, LEILA; JORDAO, MARIA T.; FRAGAS, MATHEUS G.; RUGGERI, ADRIANA; CERONI, ALEXANDRE; MICHELINI, LISETE C. Maintenance of Blood-Brain Barrier Integrity in Hypertension: A Novel Benefit of Exercise Training for Autonomic Control. FRONTIERS IN PHYSIOLOGY, v. 8, DEC 12 2017. Web of Science Citations: 11.

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