Tanshinones IIA Attenuated Oxidative Stress In Hypothalamic Paraventricular Nucleus Contribute To Sympathoexcitation In Chronic High-salt Intake Induced Hypertension

Objective:In this study, arterial blood pressure(BP) of the rats,renal sympathetic nerve activity(RSNA)and the expression of gp91 phox, angiotensin-converting enzyme(ACE), interleukin(IL)-1beta(IL-1β), interleukin(IL)-10(IL-10) in the PVN had been determined. We conducted to assess whether Tan IIA attenuats oxidative stress in the PVN and contributes to the high-salt induced hypertensive response. The results from this study will lead to a better understanding of the disease process and aid in designing new therapeutic strategies for the treatment of hypertension. Methods:Thirty two Sprague-Dawley rats which were 7 weeks old with baseline body weights between 150 and 170 grams fed with a normal salt(0.3% Na Cl) or a high salt(8% Na Cl) diet for 16 weeks. Meanwhile half of each team received Tan IIA administration or vehicle by intragastric administration. Arterial pressure was determined every 2 weeks by a tail-cuff occlusion and their recording system which was non invasively. After 16 weeks, the rats were decapitated while were under anesthesia. The PVN tissue samples were collected and stored at-80 °C for later analyses. We performed the following experimental procedures: Western blot analysis, immunofluorescence, immunofluorescence and statistical analysis. Results:There was a blunted increase in arterial blood pressure in chronic high-salt diet induced hypertension rats compared with control rats and MAP remained increased for the duration of the study. High-salt fed also induced an increase in renal sympathetic nerve activity(RSNA) compared with control rats. Reductions in MAP and RSNA values elicited by Tan IIA administration. Expression of gp91 phox and DHE were markedly higher in high-salt fed groups when compared to normal-salt fed groups. In addition, angiotensin-converting enzyme(ACE), interleukin(IL)-1β(IL-1β) in the PVN were also increased but interleukin-10(IL-10) were decreased in high salt-induced hypertensive rats. However, Tan IIA administration attenuated above changes in hypertensive rats in the immunohistochemical studies. Conclusion:These observations and the data from this study suggest that chronic and regular high-salt intake activates oxidative stress in the PVN of SD rats, and increases Sympathoexcitation and hypertensive response, which are associated with the increases of PICs, ACE in the PVN. Tan IIA improves balance between pro- and anti-inflammatory cytokines via attenuating PICs(IL-1β) and up regulating anti-inflammatory(IL-10) expression in the PVN of high salt diet–induced hypertensive rats. High-salt administration with concomitant Tan IIA treatment acts upon neurons in PVN to reduce arterial pressure and renal sympathetic nerve activity, perhaps by reducing the influence of reactive oxygen species in the region. Tan IIA may be used as a nature antioxidant to attenuated Oxidative Stress via modulating proinflammatory cytokines and reducing component of RAS in the PVN.