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Superoxide depression in the rostral ventrolateral medulla contributes to centrally antihypertensive action of moxonidine (686.31)
Author(s) -
Wang Weizhong,
Wang Yangkai,
Yu Qiang
Publication year - 2014
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.28.1_supplement.686.31
Subject(s) - moxonidine , rostral ventrolateral medulla , imidazoline receptor , endocrinology , antagonist , candesartan , angiotensin ii , chemistry , medicine , agonist , receptor , blood pressure , pharmacology , heart rate
Centrally antihypertensive action of moxonidine has been demonstrated to be resulted from activation of Imidazoline‐1 receptor (I1R) in the rostral ventrolateral medulla (RVLM). Angiotensin II (Ang II)‐derived superoxide is a major contributor to high level of blood pressure and sympathetic outflow in hypertension. The objective of the present study was to determine the effect of moxonidine on the Ang II‐derived superoxide in the RVLM of spontaneously hypertensive rat (SHR). Intracerebroventricular infusion of moxonidine (20 nmol/day, 2 wk) produced a significant decrease in blood pressure (152±4 vs 183±5 mmHg) in SHR, which can be prevented by the I1R antagonist efaroxan but not the alpha2 receptor antagonist yohimbine. Chronic treatment with moxonidine decreased the protein expression of Ang II receptor type 1 (AT1R) and NADPHase (NOX4) in the RVLM, but also blunted the cardiovascular response to microinjection of Ang II (10 pmol) into the RVLM. Production of superoxide in the RVLM was also reduced in the SHR following 2‐wk treatment with moxonidine. Moreover, it was found that subunit p50 of Nuclear Factor Kappa B (NFkB) was significantly reduced and IkB was increased in the moxonidine‐treated SHR. It is concluded that a decrease in Ang II‐AT1R‐supreoxide via NFkB pathway contributes to centrally antihypertensive action of moxonidine. This work was supported by NSFC (81170240 and 81370363).