BDNF acting in the hypothalamus induces acute pressor responses under permissive control of angiotensin II

• Published in: Autonomic neuroscience Vol. 197; pp. 1 - 8
• Main Authors: Schaich, Chris L, Wellman, Theresa L, Koi, Blanka, Erdos, Benedek
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2016
• Subjects: Advanced Basic Science; Angiotensin; Angiotensin II - metabolism; Angiotensin II Type 1 Receptor Blockers - pharmacology; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Blood pressure; Blood Pressure - drug effects; Blood Pressure - physiology; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Cardiovascular System - drug effects; Cardiovascular System - physiopathology; Hypertension - drug therapy; Hypertension - physiopathology; Male; Medical Education; Paraventricular Hypothalamic Nucleus - drug effects; Paraventricular nucleus of the hypothalamus; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1 - drug effects; Receptor, Angiotensin, Type 1 - metabolism; Sympathetic nervous system; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - physiopathology; TrkB receptors; Vasoconstrictor Agents - pharmacology; Paraventricular nucleus of the hypothalamus; TrkB receptors; Blood pressure; Brain-derived neurotrophic factor; Sympathetic nervous system; Angiotensin
• ISSN: 1566-0702; 1872-7484
• DOI: 10.1016/j.autneu.2016.02.011

Abstract Brain-derived neurotrophic factor (BDNF) expression increases in the paraventricular nucleus of the hypothalamus (PVN) during hypertensive stimuli including stress and hyperosmolarity, but its role in PVN cardiovascular regulatory mechanisms is unclear. Chronic BDNF overexpression in the PVN has been shown to elevate sympathetic tone and blood pressure in part by modulating central angiotensin (Ang) II mechanisms. However, the cardiovascular effects of short-term increases in PVN levels of BDNF and the mechanisms governing them are unknown. Therefore, we investigated whether acute BDNF microinjections into the PVN of conscious and anesthetized Sprague-Dawley rats induce blood pressure elevations and whether Ang II signaling is involved in these hypertensive responses. In conscious rats, unilateral BDNF (12.5 ng) microinjections into the PVN increased mean arterial pressure (MAP) by 27 ± 1 mm Hg ( P < 0.001 vs vehicle), which was significantly attenuated by intracerebroventricular infusion of the Ang II-type-1 receptor (AT1 R) antagonist losartan and by ganglionic blockade with intravenous hexamethonium infusion. In anesthetized rats, unilateral PVN microinjection of BDNF increased MAP by 31 ± 4 mm Hg ( P < 0.001 vs vehicle), which was prevented by PVN microinjection pretreatments with the high-affinity BDNF receptor TrkB antagonist ANA-12, losartan, the angiotensin converting enzyme inhibitor lisinopril, or by intravenous hexamethonium. Additional experiments in hypothalamic samples including the PVN revealed that BDNF-induced TrkB receptor phosphorylation was prevented by ANA-12 and losartan pretreatments. Collectively, these data indicate that BDNF acting within the PVN acutely raises blood pressure under permissive control of Ang II-AT1 R mechanisms and therefore may play an important role in mediating acute pressor responses to hypertensive stimuli.