Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Higashi-ku, Fukuoka, Japan.
J Hypertens. 2012 Sep;30(9):1758-65. doi: 10.1097/HJH.0b013e32835613d7.
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.
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.
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.
脑桥头端腹外侧区（RVLM）和下丘脑室旁核（PVN）参与高血压的神经机制。RVLM 中的氧化应激导致增强的中枢交感传出，导致高血压实验模型（如自发性高血压大鼠（SHR））中的高血压。我们研究了 SHR 中 PVN 和 RVLM 中的氧化应激对血压（BP）调节的相对贡献。
我们将编码锰超氧化物歧化酶基因（AdMnSOD）或β-半乳糖苷酶基因（AdLacZ）的腺病毒载体双侧转染到 RVLM 或 PVN。使用无线电遥测系统监测平均动脉压（MAP）和心率（HR）。与 Wistar-Kyoto 大鼠相比，SHR 的 PVN 中的氧化应激水平通过硫代巴比妥酸反应物质评估得到增强，并且与非转染的 SHR 相比，MnSOD 转染降低了氧化应激水平。与 AdLacZ-RVLM 转染的 SHR 相比，AdMnSOD-RVLM 转染的 SHR 的 MAP 和 HR 降低。相比之下，与 AdLacZ-PVN 转染的 SHR 相比，AdMnSOD-PVN 转染的 SHR 的 MAP 没有降低，但 HR 降低。MnSOD 转染到 SHR 的 RVLM 和 PVN 均降低了 MAP，并引起 HR 的明显降低。
这些发现表明，PVN 中的氧化应激抑制降低了 SHR 的 HR，但不降低 BP，并且与 RVLM 相互作用进一步降低了 HR，但不降低 BP。综上所述，PVN 和 RVLM 中的氧化应激在 SHR 的心血管调节中发挥不同的作用。
