Oxidative stress in the sympathetic premotor neurons contributes to sympathetic activation in renovascular hypertension.

BACKGROUND: Based on previous data, we hypothesized that an increase of angiotensin II (Ang II)-via the Ang II type 1 (AT-1) receptor-in the rostral ventrolateral medulla (RVLM) and the paraventricular nucleus (PVN) of the hypothalamus could activate NAD(P)H oxidase that will produce superoxides resulting in increased sympathetic activity and hypertension.

METHODS: The mRNA expression of AT-1 receptors, NAD(P)H oxidase subunits (p47phox and gp91phox), and CuZnSOD were analyzed in the RVLM and PVN of male Wistar rats (Goldblatt hypertension model, 2K-1C). In addition, we administered Tempol 1 and 5 nmol into the RVLM, PVN, or systemically. The mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were analyzed.

RESULTS: The AT-1 mRNA expression and NAD(P)H oxidase subunits was greater in the RVLM and PVN in 2K-1C compared to the control group. Furthermore, the CuZnSOD expression was similar in both groups. Tempol 1 nmol into the RVLM reduced MAP (15 +/- 1%) and RSNA (11 +/- 2%) only in 2K-1C rats. Tempol (5 nmol) in the same region decreased the MAP (12 +/- 4%) and RSNA (20 +/- 7%), respectively, only in 2K-1C. In the PVN, Tempol 5 nmol resulted in a significant fall in the MAP (24 +/- 1%) and in the RSNA (7.9 +/- 2%) only in the 2K-1C. Acute intravenous (IV) infusion of Tempol decreased MAP and RSNA in the 2K-1C but not in the control rats.

CONCLUSIONS: The data suggest that the hypertension and sympathoexcitation in 2K-1C rats were associated with an increase in oxidative stress within the RVLM, the PVN and systemically.