Oxidative Stress in the Sympathetic Premotor Neurons Contributes to Sympathetic Activation in Renovascular Hypertension

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Oliveira-Sales, Elizabeth B. [UNIFESP]
Nishi, Erika E. [UNIFESP]
Carillo, Bruno A. [UNIFESP]
Boim, Mirian A. [UNIFESP]
Dolnikoff, Miriam S. [UNIFESP]
Bergamaschi, Cassia T. [UNIFESP]
Campos, Ruy R. [UNIFESP]
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BACKGROUNDBased 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.METHODSThe 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.RESULTSThe 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.CONCLUSIONSThe 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.
American Journal of Hypertension. New York: Nature Publishing Group, v. 22, n. 5, p. 484-492, 2009.