Journal
AMERICAN JOURNAL OF HYPERTENSION
Volume 21, Issue 1, Pages 98-104Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ajh.2007.12
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BACKGROUND Oxidative stress is a state in which excess reactive oxygen species (ROS) overwhelm endogenous antioxidant systems. It is known that this state has been involved in the development of hypertension. On the basis of previous data, we hypothesized that overactivity of NAD(P)H oxidase-derived ROS and the lowered activity of CuZnSOD, an endogenous antioxidant within the rostral ventrolateral medulla (RVLM), could contribute to 2K-1C (two-kidney one-clip) hypertension. Moreover, to test the functional significance of whether oxidative stress was involved in the maintenance of sympathetic vasomotor tone and blood pressure in 2K-1C hypertension, we administered Ascorbic Acid (Vit C), an antioxidant, into the RVLM or systemically. METHODS Experiments were performed in male Wistar rats (6 weeks after renal surgery - Goldblatt hypertension model - 2K-1C. The mRNA expression of NAD(P)H oxidase subunits (p47phox and gp91 phox) and CuZnSOD were analyzed in the RVLM using real-time PCR technique. The mean arterial blood pressure, heart rate, and renal sympathetic nerve activity were analyzed. Blood samples were collected and measured using thiobarbituric acid-reactive substances (TBARS). RESULTS The mRNA expression of NAD(P)H oxidase subnits (p47 phox and gp9l pox) was greater in 2K-1C compared to the control group in the RVLM, and CuZnSOD expression was similar in both groups. In the RVLM, Vit C resulted in a fall in arterial pressure and in the sympathetic activity only in the 2K-1C rats. Thiobarbituric acid-reactive substances (TBARS) were significantly greater in 2K-1C rats and the acute infusion of Vit C significantly decreased arterial pressure and renal sympathetic activity in 2K-1C. CONCLUSIONS The results support the idea that an increase in oxidative stress within the RVLM and systemically plays a major role in maintaining high arterial blood pressure and sympathetic drive in 2K-1C hypertension.
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