Different role of oxidative stress in paraventricular nucleus and rostral ventrolateral medulla in cardiovascular regulation in awake spontaneously hypertensive rats.
OBJECTIVE
The rostral ventrolateral medulla (RVLM) of the brainstem and the paraventricular nucleus of the hypothalamus (PVN) are involved in the neural mechanisms of hypertension. Oxidative stress in the RVLM contributes to the enhanced central sympathetic outflow that leads to hypertension in experimental models of hypertension, such as spontaneously hypertensive rats (SHRs). We investigated the relative contribution of oxidative stress in the PVN and RVLM of SHR in blood pressure (BP) regulation.


RESULTS
We transfected adenovirus vectors encoding the manganese superoxide dismutase gene (AdMnSOD) or β-galactosidase gene (AdLacZ) bilaterally into the RVLM or PVN. Mean arterial pressure (MAP) and heart rate (HR) were monitored using a radiotelemetry system. Oxidative stress levels in the PVN of SHR evaluated by thiobarbituric acid-reactive substances were enhanced compared with those of Wistar-Kyoto rats and reduced by MnSOD transfection compared with nontransfected SHR. MAP and HR of AdMnSOD-RVLM-transfected SHR were decreased compared with AdLacZ-RVLM-transfected SHR. In contrast, MAP of AdMnSOD-PVN-transfected SHR was not decreased compared with AdLacZ-PVN-transfected SHR, but HR was decreased compared with AdLacZ-PVN-transfected SHR. MnSOD transfection into both the RVLM and PVN of SHR decreased MAP and elicited a profound decrease in HR.


CONCLUSIONS
These findings indicate that inhibition of oxidative stress in the PVN decreases HR, but not BP in SHR, and elicits a further decrease in HR, but not BP, by interacting with the RVLM. Taken together, the oxidative stress in the PVN and RVLM plays a different role for cardiovascular regulation in SHR.
Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Higashi-ku, Fukuoka, Japan.
Masaaki
M
Nishihara
Yoshitaka
Y
Hirooka
Takuya
T
Kishi
Kenji
K
Sunagawa
D000818:Animals; D001794:Blood Pressure; D015153:Blotting, Western; D002319:Cardiovascular System / Q000503:physiopathology*; D006339:Heart Rate; D007150:Immunohistochemistry; D008297:Male; D018384:Oxidative Stress; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013482:Superoxide Dismutase / Q000235:genetics; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014162:Transfection; D001616:beta-Galactosidase / Q000235:genetics
D017392:Thiobarbituric Acid Reactive Substances; D013482:Superoxide Dismutase; D001616:beta-Galactosidase