Abstract 14355: Inhibition of ROS in the Rostral Ventrolateral Medulla Improves Baroreflex Function in Stroke-Prone Spontaneously Hypertensive Rats
Background: Previous studies suggest that the increased reactive oxygen species (ROS) in the rostral ventrolateral medulla (RVLM), a vasomotor center in the brainstem, contributes to sympathoexcitation. It has been well established that cardiovascular diseases often impair baroreflex.
Hypothesis: The aim of the present study was to determine whether the inhibition of ROS in the RVLM by the overexpression of Mn superoxide dismutase (MnSOD) improves baroreflex function and to determine the process of change between baroreflex sensitivity (BRS) and blood pressure (BP) or heart rate (HR) in stroke-prone spontaneously hypertensive rats (SHRSP).
Methods and Results: We inhibited ROS production in the RVLM by transfecting adenovirus vectors encoding either MnSOD (AdMnSOD) or β-galactosidase (Adβgal) into the RVLM. Baroreflex sensitivity (spontaneous sequence method) was significantly lower in untreated-SHRSP than in Wistar-Kyoto rats (WKY) (1.66±0.02 vs. 2.15±0.06 ms/mmHg, p<0.01, n=7 for SHRSP, n=3 for WKY). BRS was significantly higher in AdMnSOD-treated SHRSP than in Adβgal-treated SHRSP at day 3 after the gene transfer. And mean arterial pressure (MAP) and HR in a conscious state were significantly lower in AdMnSOD-treated SHRSP than in Adβgal-treated SHRSP at day 5 after the gene transfer. The BRS increased, and MAP and HR reduced overtime. The MnSOD transfection, relative to Adβgal, lowered MAP and HR and increased BRS. These changes peaked at day 7 after the transfection (ΔBRS; +1.85±0.10 ms/mmHg, ΔMAP; -38.3±4.6 mmHg, ΔHR; -77.4±6.4 bpm, n=5). In non-treated SHRSP, intravenous infusions of metoprorol increased BRS whereas atropine did not. In contrast, in AdMnSOD-treated SHRSP, atropine decreased BRS whereas metoprorol did not.
Conclusion: These results indicate that ROS in the RVLM impairs BRS via activation of sympathetic nervous system. Second, our findings suggest that the improved BRS is due to the inhibition of the activity of the sympathetic nervous system, but not activation of the parasympathetic nervous system.
- © 2011 by American Heart Association, Inc.