Abstract 13626: Aerobic Training Corrects Bbb Dysfunction Within Preautonomic Areas In Heart Failure Rats By Normalizing The Augmented Transcytosis

Abstract

Introduction: Besides intense renin-angiotensin system activation and sympathoexcitation, heart failure (HF) is accompanied by marked autonomic dysfunction. We showed previously in hypertensive rats that blood-brain barrier (BBB) dysfunction in preautonomic areas aggravated the autonomic dysfunction but is corrected by aerobic training (T). There is no information in HF Hypothesis: We hypothesized that BBB dysfunction within the paraventricular hypothalamic nucleus (PVN) contributes to the autonomic imbalance, which may be ameliorated by T Methods: Wistar rats were submitted to anterior descending coronary artery occlusion or Sham surgery and echocardiography. Four weeks later, HF (ejection fraction≤40%) and Sham rats underwent a T (55% of maximal exercise capacity) or sedentary (S) protocol for 8 weeks and were chronically cannulated for hemodynamic/autonomic recordings and determination of BBB permeability (intra-arterial injection of fluorescent dyes with high and low molecular weight). To investigate the mechanisms underlying HF- and T-induced BBB changes, the PVN was harvested and processed for transmission electron microscopy Results: HF-S exhibited reduced arterial pressure (AP, -10%), increased sympathetic activity to vessels and heart (+45% on average), decreased spontaneous baroreflex sensitivity (BrS, -19%), large increase in systolic AP variability (+53%), and 4-fold increase in PVN BBB leakage (11.3±1.4 vs. 2.8±0.2 %area in Sham-S). HF-S also exhibited increased transcytotic vesicles (+80%) in PVN capillaries’ endothelium, without any change in tight junctions’ expression, capillary diameter, and pericytes’ coverage. These changes were completely normalized in HF-T rats. In Sham rats T only caused resting bradycardia, increased BrS, and a mild reduction of transcytotic vesicles and PVN leakage. There were significant correlations between the number of transcytotic vesicles x PVN BBB leakage (Y=0.82x -1.74, r 2 =0.843, P<0.001) and BBB leakage x sympathetic activity (Y=0.66x +4.37, r 2 =0.415, P<0.001) Conclusions: HF courses with PVN BBB dysfunction, which is due to increased transcytosis without changes in the paracellular pathway. Training ameliorates HF’s autonomic control by normalizing transcytosis