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Genetic knockdown of brain-derived neurotrophic factor in the nervous system attenuates angiotensin II-induced hypertension in mice
Journal article   Open access   Peer reviewed

Genetic knockdown of brain-derived neurotrophic factor in the nervous system attenuates angiotensin II-induced hypertension in mice

Zhongming Zhang, Yijing Zhang, Yan Wang, Shengchen Ding, Chenhui Wang, Li Gao, Alan Johnson and Baojian Xue
Journal of the renin-angiotensin-aldosterone system, Vol.20(1), pp.1470320319834406-9
01/2019
DOI: 10.1177/1470320319834406
PMCID: PMC6429654
PMID: 30894041
url
https://doi.org/10.1177/1470320319834406View
Published (Version of record) Open Access

Abstract

Brain-derived neurotropic factor (BDNF) is expressed throughout the central nervous system and peripheral organs involved in the regulation of blood pressure, but the systemic effects of BDNF in the control of blood pressure are not well elucidated. We utilized loxP flanked BDNF male mice to cross with nestin-Cre female mice to generate nerve system BDNF knockdown mice, nestin-BDNF (+/-), or injected Cre adenovirus into the subfornical organ to create subfornical organ BDNF knockdown mice. Histochemistry was used to verify injection location. Radiotelemetry was employed to determine baseline blood pressure and pressor response to angiotensin II (1000 ng/kg/min). Real-time polymerase chain reaction was used to measure the expression of renin-angiotensin system components in the laminal terminalis and peripheral organs. Nestin-BDNF (+/-) mice had lower renin-angiotensin system expression in the laminal terminalis and peripheral organs including the gonadal fat pad, and a lower basal blood pressure. They exhibited an attenuated hypertensive response and a weak or similar modification of renin-angiotensin system component expression to angiotensin II infusion. Subfornical organ BDNF knockdown was sufficient for the attenuation of angiotensin II-induced hypertension. Central BDNF, especially subfornical organ BDNF is involved in the maintenance of basal blood pressure and in augmentation of hypertensive response to angiotensin II through systemic regulation of the expression of renin-angiotensin system molecules.
Angiotensin II Animals Blood Pressure Brain-Derived Neurotrophic Factor - metabolism Gene Knockdown Techniques Hypertension - metabolism Hypertension - physiopathology Male Mice Nervous System - metabolism Nestin - metabolism Renin-Angiotensin System Subfornical Organ - metabolism

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