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Chronic Superoxide Signaling in the Rostral Ventrolateral Medulla (RVLM) is Essential For Goldblatt Hypertension
Author(s) -
OliveiraSales Elizabeth B,
Colombari Debora SA,
Davisson Robin L,
Kasparov Sergey,
Campos Ruy R,
Paton Julian FR
Publication year - 2010
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.24.1_supplement.809.3
Subject(s) - rostral ventrolateral medulla , medicine , superoxide , endocrinology , reactive oxygen species , superoxide dismutase , nadph oxidase , pathogenesis , blood pressure , chemistry , heart rate , oxidative stress , enzyme , biochemistry
Reactive oxygen species (ROS) in peripheral cardiovascular tissues are implicated in the pathogenesis of Goldblatt (two kidney one clip, 2K1C) hypertension. We identified an imbalance between ROS generation and oxidant scavenging in the RVLM of Goldblatt rats. In 2K1C rats, the RVLM exhibited increased mRNA expression of NAD(P)H oxidase subunits. With a role in sympathetic activity generation, we tested whether chronic superoxide scavenging in RVLM would affect Goldblatt hypertension. In Wistar rats (male, 150–180g) superoxide dismutase was over expressed (Ad‐CMV‐CuZnSOD) chronically using an adenoviral vector 3 weeks after renal artery clipping. In 2K1C rats, the elevated AP and heart rate returned to control values one week after transfection, was maintained for 3 weeks and associated with decreased low frequency spectra of systolic blood pressure variability. We confirmed both reduced ROS levels and the presence of CuZnSOD in RVLM neurons immunohistochemically. No changes in arterial pressure were observed in control rats receiving Ad‐CMV‐eGFP in the RVLM. Thus, chronic superoxide signaling in the RVLM of the Goldblatt model is essential for the hypertension. Supported by CAPES and British Heart Foundation.