Paraventricular Nucleus Infusion of Astaxanthin Attenuates Hypertension by Modulating Cytokines and Attenuating the Rennin angiotensin System in Spontaneously Hypertensive Rats

[Speaker] Xiaolian Shi:1
[Co-author] Hong-Li Gao:2, Jie Qi:2, Xiao-Jing Yu:2, Kai-Li Liu:2, Yan-Mei Chen:2, Yu-Ming Kang:2
1:Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China, 2:Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Cardiovascular Research Center, Xi'an Jiaotong University Health Science Center, China

Background Previous findings from our laboratory and others indicate that oxidative stress and inflammatory reaction play an important role in the development of hypertension. The aim of this study was to investigate the effects of astaxanthin, a strong antioxidant, through hypothalamic paraventricular nucleus infusion in spontaneously hypertensive rats and the underlying mechanism. Methods Spontaneously hypertensive rats (SHR) rats were received bilateral PVN infusion astaxanthin at 20 mugs per hour via osmotic minipump for 4 weeks. Mean arterial pressure was recorded by a tail-cuff occlusion method once a week. Renal sympathetic nerve activity (RSNA) was recorded before sacrifice. Oxygen free radicals was evaluated by DHE staining and subunits of NAD(P)H oxidase by immunofluorescence and western blot in PVN. Levels of cytokines, ACE and angiotensin 2 type1 receptor (AT1-R) were also measured either by IF and or by WB in PVN. Results Spontaneously hypertensive rats exhibited significantly higher mean arterial pressure and RSNA. These rats also showed oxidative stress and higher pro-inflammatory cytokines in PVN. PVN infusion with astaxanthin significantly decreased MAP and RSNA compared with WKY rats. Results from immunofluorescence and western blot revealed that Aastaxanthin inhibited oxidative stress through decreasing NOX-2, NOX-4 (subunits of NAD(P)H oxidase) expression, and strengthening Cu-Zn SOD and Mn SOD activity in the PVN. It also showed that Astaxanthin significantly attenuated the levels of IL-1beta, IL-6, MCP-1, ACE and AT1-R, increased the levels of IL-10 in PVN. Conclusions These results imply that PVN infusion of astaxanthin has protective effects on hypertension by attenuating oxidative stress and modulating RAS components and pro inflammatory cytokines and anti inflammatory cytokines.
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