Abstract 034: Opposite Effects of Hypertension and Training on Blood Brain Barrier Integrity in Autonomic Areas of the Spontaneously Hypertensive Rat
It is well known that chronic hypertensive rats exhibit deficient blood brain barrier (BBB). We evaluate age-induced progression of BBB lesion in autonomic areas of the SHR and the possible effect of aerobic training on BBB integrity. SHR aged 1, 3 and 5 month were chronically cannulated for hemodynamic recordings in the conscious state (femoral), followed by anesthesia and dextrans’ infusion (FITC-10kDA + RHO-70kDA, carotid artery). Twenty minutes later rats were sacrificed, brains were removed, post-fixed and cryoprotected. BBB permeability was evaluated in sequential 30 μm slices of the hypothalamic paraventricular nucleus (PVN), nucleus tractus solitarii (NTS) and rostroventrolateral medulla (RVLM) by the capability of FITC10 to leak into the brain parenchyma (in % area/area of interest, fluorescent microscope, ImageJ analysis). Other 3-months old SHR were submitted to treadmill training (T=55% of maximum capacity, 1h/day, 5 d/week) or kept sedentary for 8 weeks. Age-matched WKY served as control. Although SHR aged 1 month were normotensive and exhibited no BBB leakage (0.02±0.01 to 0.15±0.03% in all areas, values similar to WKY), leakage augmented sharply with the establishment of hypertension (average of 8.1±0.7% in SHR-3mo, 9.3±1.2% in SHR-5mo). In the WKY, there was only a small age-induced increase in BBB leakage (average of 0.63±0.05% in PVN, NTS and RVLM). Interestingly T promptly reduced dye leakage in the 3 autonomic areas of the SHR (~1.0±0.2% from 2 up to 8 weeks of training) without changing the leakage in PVN, NTS and RVLM of WKY rats and within the hypoglossus nucleus of the SHR (a non-autonomic area). T-induced improvement of BBB integrity in autonomic areas of the SHR were accompanied by significant reductions of HR (-10%) and MAP (-13%), increased HR variability (+2.1-fold), decreased pressure variability (-49%) and increased spontaneous baroreflex sensitivity (+2.3-fold). Data show that BBB lesion in SHR is caused by the establishment of hypertension and that T improves perfusion of autonomic brain areas in hypertensive individuals by preserving BBB integrity. This adaptive response is crucial for a near normal neuronal activity, thus normalizing autonomic control of the circulation even in the presence of hypertension.
Author Disclosures: L.C. Michelini: None. M.T. Jordao: None. A. Ceroni: None. L. Buttler: None.
- © 2015 by American Heart Association, Inc.