Reactive Oxygen Species In The Paraventricular Nucleus Mediate Sympathetic Overactivity In Hypertension Rats

BackgroundHypertension is a common cardiovascular system disease that seriously threaten tohuman’s health. It is well known that the sympathetic overactivity is one of theimportant characteristics of hypertension, and it plays a key role in the pathogenesis,progression and damaging the target organ of hypertension. But the central mechanismof hypertension remains unclear. The paraventricular nucleus (PVN) is an importantnuclei which integrates cardiovascular activity. The dysfunction of PVN may be animportant reason for the sympathetic overactivity in hypertension. The reactive oxygenspecies (ROS) is a metabolite of oxygen and as one of the signaling molecules involvesin the occurrence and maintenance of the hypertension. We concluded that there wasclose relationship between the abnormal increased ROS and sympathetic overactivity ofhypertension.ObjectiveTo investigate the effects of ROS in the PVN mediated sympathetic overactivity intwo-kindney, one-clip (2K1C) hypertension rats and search the molecular targets ofantihypertensive effects. By intervening these targets, That the therapeutic action ofantihypertensive drugs will be observed, and these providing the scientific experimentsand theoretical basis for the prevention and treatment of hypertension.MethodsAccording to the technique of Goldblatt2K1C established renovascularhypertension rat model. The conscious noninvasive method with tail cuff was performedin rats to record the systolic blood pressure (SBP). The activity of superoxidedismutase(SOD) was determined in Xanthine oxidase, Using the method of thiobarbituric acid to measure the concentration of MDA. Arterial pressure(ABP), meanarterial pressure (MAP), heat rate (HR) and renal sympathetic nerve activity (RSNA)were simultaneously recorded in vivo on powerlab data-acquisiton systems. The PVNwas determined by brain stereotaxic instrument according to the Paxinos and Watson ratatlas and the medicines were microinjected into the PVN after taking baroreceptordenervation away and cutting vagotomy off in the anesthetized rats.Result1. The SBP, MAP and RSNA in2K1C rats were significantly higher than Sham rats.2. The activity of SOD decresased notably and the concentration of MDA increasedsignificantly in2K1C rats.3. Bilateral microinjection of superoxide anion scavenger Tempol（0.2mol/L）into thePVN decreased the MAP and RSNA in both2K1C and Sham rats, but the MAPresponse of2K1C was greater than that of sham.4. Bilateral microinjection of NADPH oxidase inhibitor APO or DPI （0.01mol/L）intothe PVN decreased the MAP and RSNA in both2K1C and Sham rats, but the MAPresponse of2K1C was greater than that of sham.5. Bilateral microinjection of SOD inhibitor DETC（0.1mol/L）into the PVN increasedthe MAP and RSNA in both2K1C and Sham rats, but the MAP response of2K1C wasgreater than that of sham.Conclusion1. The RSNA was significantly enhanced in2K1C.2. The level of ROS in the PVN was significantly elevated in2K1C.3. ROS in the PVN associated with sympathetic overactivity and the development of2K1C hypertension.