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Brain (pro)renin receptor knockdown modulates the body fluid homeostasis during angiotensin II‐dependent hypertension
Author(s) -
Cao Theresa,
Li Wencheng,
Seth Dale,
Feng Yumei
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.906.20
Subject(s) - medicine , endocrinology , gene knockdown , homeostasis , excretion , renin–angiotensin system , chemistry , angiotensin ii , receptor , plasma renin activity , blood pressure , apoptosis , biochemistry
We previously reported that brain‐targeted PRR knockdown attenuates Angiotensin (Ang) II‐dependent hypertension and decreases vasopressin (AVP) release. To address the role of PRR in body fluid homeostasis, adeno‐associated virus‐mediated PRR shRNA (AAV‐PRR‐shRNA) was intracerebroventricularly injected to non‐transgenic (NT, n = 5) and human renin and angiotensinogen transgenic (RA, n= 6) mice. Urine excretion and water intake were recorded using metabolic cages. Ang II levels were measured at baseline and two weeks after PRR knockdown. At baseline, RA mice exhibited higher water intake (5 ± 0.6 VS. 3 ± 0.5 mL/day, p< 0.05), urine excretion (3.3 ± 0.5 VS 1.9 ± 0.1mL/day, p< 0.05), and urinary sodium excretion (0.3 ± 0.1 VS. 0.1 ± 0.1mmol/day, p< 0.05) compared to NT mice. PRR knockdown decreased water intake (3.3 ± 0.6 mL/day, p< 0.05) and urinary sodium excretion (0.2 ± 0.1mmol/day, p< 0.05) in RA mice. In addition, PRR‐shRNA significantly decreased Ang II levels in both the hypothalamus (1470 ± 90 VS. 1051 ± 77 fmol/mg, p< 0.05) and plasma (347 ± 41 VS. 156 ± 42 fmol/ml, p< 0.05) compared to baseline in RA mice; however, it did not alter Ang II levels in NT mice. This data indicates that brain‐targeted PRR knockdown modulates the body fluid homeostasis and is associated with reduction of Ang II levels, and brain PRR plays a regulatory role in the body fluid homeostasis during Ang IIdependent hypertension.