Inhibition of Oxidative Stress in Rostral Ventrolateral Medulla Improves Impaired Baroreflex Sensitivity in Stroke-Prone Spontaneously Hypertensive Rats

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  • Ogawa Kiyohiro
    Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Science
  • Hirooka Yoshitaka
    Department of Advanced Cardiovascular Regulation and Therapeutics, Kyushu University Graduate School of Medical Science
  • Shinohara Keisuke
    Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Science
  • Kishi Takuya
    Department of Advanced Therapeutics for Cardiovascular Diseases, Kyushu University Graduate School of Medical Science
  • Sunagawa Kenji
    Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Science

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Reactive oxygen species (ROS) in rostral ventrolateral medulla (RVLM) of brainstem contribute to sympathoexcitation and are critically involved in the pathogenesis of hypertension. Baroreflex sensitivity (BRS) is a valuable prognostic parameter of the autonomic nervous system, and is impaired in hypertension. The aim of the present study was to determine whether or not a chronic reduction of ROS in the RVLM improves impaired BRS in hypertensive rats. We transfected adenovirus vectors encoding either manganese superoxide dismutase (AdMnSOD) or β-galactosidase (AdLacZ) into the RVLM of stroke-prone spontaneously hypertensive rats (SHRSP). We measured BRS using the spontaneous sequence method. BRS was significantly lower in SHRSPs than in Wistar-Kyoto rats. In the AdMnSOD-transfected SHRSP, blood pressure, heart rate, and sympathetic nervous system activation were significantly decreased from day 5 after the gene transfer. BRS in the AdMnSOD-transfected SHRSP was significantly increased from day 4 after the gene transfer with the reduction of ROS in the RVLM. Furthermore, in the AdMnSOD-transfected SHRSP, intravenous infusion of atropine dramatically decreased BRS. In contrast, in the AdLacZ-transfected SHRSP, atropine did not decrease BRS. These results suggest that chronic reduction of ROS in the local RVLM improves the impaired BRS in SHRSP through inhibition of the sympathetic component.

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