BDNF-mediated depressor response by direct baroreceptor activation benefits for prevention and control of hypertension in high-latitude cold region

Abstract

Brian-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) signaling impacts on neuronal and cardiovascular physiology; however, its role in neurocontrol of circulation via baroreflex afferent pathway is largely unknown. Gene and protein expression of BDNF/TrkB were detected in the nodose (NG) and nucleus of tractus solitary (NTS) and expression levels were higher in male compared with female rats, which is relevant well with the blood pressure (BP, males > females in average). Microinjection of BDNF into NG dose-dependently reduced BP and this reduction was more dramatic in shamed control vs. renovascular hypertension (RVH) model rats, which partially inhibited in the presence of TrkB inhibitor K252a, indicating that BDNF-TrkB tends to lower BP under physiological and hypertensive conditions due presumably to a negative feed-back control by BP or compensatory mechanism. To answer this question, expression profiles for BDNF-TrkB were tested in the tissue of NG and NTS collected from RVH model rats. Consistently, the expression of both BDNF-TrkB were significantly up-regulated in RVH model alone with the elevation of BP. Taken these data together, our observation provides direct evidence showing the fundamental role of BDNF-TrkB signaling in autonomic control of BP regulation through baroreflex afferent function, potentially dominant role of BDNF-TrkB-mediated BP reduction in vivo baroreceptor activation due to distinct cellular mechanism compared with their role in the NTS, which extends our understanding of activity-dependent or compensatory mechanism of BDNF-TrkB in response to BP change, and sheds new light of BDNF-TrkB as potential target in prevention and control of hypertension in cold-region.