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.
Oliveira-Sales
Elizabeth B
EB
Cardiovascular Division, Department of Physiology, Federal University of São Paulo, São Paulo, Brazil.
Nishi
Erika E
EE
Carillo
Bruno A
BA
Boim
Mirian A
MA
Dolnikoff
Miriam S
MS
Bergamaschi
Cássia T
CT
Campos
Ruy R
RR
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D009046:Motor Neurons / Q000502:physiology; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*
D003497:Cyclic N-Oxides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D013113:Spin Labels; D000804:Angiotensin II; D013482:Superoxide Dismutase; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; C001803:tempol