BDNF acting in the hypothalamus induces acute pressor responses under permissive control of angiotensin II.
BDNF acting in the hypothalamus induces acute pressor responses under permissive control of angiotensin II.
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DOI：
10.1016/j.autneu.2016.02.011
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发表时间：
2016-05
影响因子：
2.7
通讯作者：
Erdos, Benedek
中科院分区：
文献类型：
--
作者：
Schaich, Chris L.;Wellman, Theresa L.;Koi, Blanka;Erdos, Benedek
关键词：
脑源性神经营养因子(BDNF)在包括应激和高渗在内的高血压刺激下在下丘脑室旁核(PVN)中的表达增加，但其在PVN心血管调节机制中的作用尚不清楚。慢性脑源性神经营养因子在室旁核的过度表达被证明部分通过调节中枢血管紧张素(Ang)II机制来升高交感神经张力和血压。然而，短期增加脑源性神经营养因子的PVN水平对心血管的影响及其调控机制尚不清楚。因此，我们研究了清醒和麻醉的SD大鼠PVN内微量注射BDNF是否会引起血压升高，以及Ang II信号是否参与了这些高血压反应。在清醒大鼠的下丘脑室旁核内微量注射脑源性神经营养因子(12.5 ng)，平均动脉压(MAP)增加27±1 mm Hg(P<；0.001 vs VS)，这种作用可被脑室注射血管紧张素II-1型受体拮抗剂氯沙坦和神经节阻滞剂六甲溴铵所显著减弱。在麻醉大鼠，单侧室旁核微量注射脑源性神经营养因子可使MAP升高31±4 mm Hg(P<；0.001)，这可被高亲和力脑源性神经营养因子受体TrkB拮抗剂氯沙坦、血管紧张素转换酶抑制剂赖诺普利或静脉注射六甲溴胺所阻断。在下丘脑样本包括室旁核的其他实验表明，ANA-12和氯沙坦预处理可以阻止BDNF诱导的TrkB受体磷酸化。综上所述，这些数据表明，在Ang II-AT1R机制的许可控制下，在PVN内作用的BDNF可以显著升高血压，因此可能在介导对高血压刺激的急性升压反应中发挥重要作用。
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 (AT1R) 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-AT1R mechanisms and therefore may play an important role in mediating acute pressor responses to hypertensive stimuli.
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