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The Effects of Smooth Muscle‐Targeted Nox1‐Overexpression in the Development of Hypoxia‐Mediated Pulmonary Hypertension
Author(s) -
Reed Alana Leigh,
Griendling Kathy K.,
Elms Shawn C.,
Sutliff Roy L.
Publication year - 2006
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.20.4.a402-a
Subject(s) - hypoxia (environmental) , pulmonary hypertension , nox1 , cardiology , medicine , chemistry , nadph oxidase , oxygen , oxidative stress , organic chemistry
Pulmonary hypertension (PH) is characterized by proliferation and migration of vascular smooth muscle cells, increased right ventricular pressure (RVP), right heart hypertrophy, and eventually right‐sided heart failure. Chronic hypoxia is a well‐established cause of the disease; furthermore, reactive oxygen species (ROS) such as superoxide have been implicated in the development of PH. One important source of ROS in the vasculature is the NAD(P)H oxidases. Here, we use a mouse model which overexpresses Nox1, the catalytic subunit of the vascular NAD(P)H oxidase, in smooth muscle. Mice were housed in a hypoxia chamber, inspiring 10% O 2 for five weeks to induce PH. RVP was measured using a pressure‐transducing catheter inserted into the right jugular and advanced into the right ventricle. Hypertrophy was assessed by measuring the mass ratio of the RV to the LV plus septum. Hypoxia increased hematocrit levels in both wild‐type (WT) and Nox1 mice. Exposure to hypoxia increased the RV/LV ratio for WT mice from 0.30 ± 0.01 to 0.40 ± 0.02 and for Nox1 mice from 0.28 ± 0.01 to 0.43 ± 0.02 ( P <0.005; n=4). In WT mice the RVP was increased from 38.0 ± 3.68 mmHg to 51.7 ± 4.93 mmHg, but no change was observed for Nox1 mice. These preliminary data establish that hypoxia causes right ventricular hypertrophy in both WT and Nox1 mice while RVP is only increased in WT mice and not in Nox1 mice. Therefore, this model may be useful in elucidating the differences between hypertrophic and hemodynamic changes that occur in the development of PH. This research was supported by HL070892 to RS.