Sex Differences in Central Neural Activation During Acute Hypernatremia

项目总结/摘要 与血压有关的疾病仍然是两性面临的一个重大公共卫生挑战。男性 与女性相比，高血压患病率较高，直到60岁左右，之后患病率较高， 女性，反映了女性性激素的心脏保护作用。成人高血压的高发率 与高钠饮食摄入有关因此，研究对钠反应的性别差异可能 对理解男女之间的这些健康差异很重要。中枢钠感知是 在介导对与高盐摄入相关的相对高钠血症的神经激素反应中至关重要。的 室周器官（CVO），包括终板血管器（OVLT）和穹窿下 但是，脑内的神经元缺乏完整的血脑屏障，并且含有能够感知变化的神经元。 血液中的钠浓度。CVOs还介导钠诱导的交感神经变化 活动（SNA）、加压素（AVP）、口渴和BP。对人类的研究表明， 在急性高钠血症（高渗盐水输注）期间，这与未被充分认识的相对 高钠血症是由高钠摄入引起的。然而，没有人类研究调查是否有 急性高钠血症时中枢神经激活的性别差异。因此，本提案的重点 目的是研究钠敏感脑区（SFO，OVLT）功能连接的性别差异， 参与交感神经流出的脑区（延髓头端腹外侧（RVLM）、孤束核 (NTS)在急性高钠血症期间（通过高渗盐水输注）， 血氧水平依赖（BOLD）fMRI。我们还将评估这些反应是否与 AVP、去甲肾上腺素（NE）、口渴和BP的变化。该提案涉及两个具体目标：目标1将评估 钠敏感脑区（SFO，OVLT）之间功能连接变化的性别差异;目的2 将评估交感神经调节脑区之间功能连接变化的性别差异 (RVLM、NTS、CVLM）。我们假设急性高钠血症会增加 钠敏感脑区（目标1），并增加与RVLM的连接，减少与RVLM的连接。 新界南运输系统及新界南车辆管理系统（目标2）。我们假设，男性将有更大的反应，因为（1）在盐敏感 在啮齿动物模型中，雄性动物显示动脉血压的变化较大;（2）男性在反应中有较大的AVP释放 高渗盐水输注;（3）男性有更大的MSNA，BP和前脑BOLD fMRI反应， 各种心血管压力源这一建议有可能提供重要的见解性别特异性 BP调节和液体平衡机制，并将为学员提供BOLD的具体指导 功能磁共振成像和技术写作，这是他发展成为一个多产的研究科学家的关键。

PROJECT SUMMARY/ABSTRACT Blood pressure (BP)-related diseases continue to be a major public health challenge in both sexes. Men have a higher prevalence of hypertension compared to women until about age 60, after which prevalence is greater in women, reflecting the cardioprotective role of female sex hormones. The high incidence of hypertension in adults is associated with high dietary sodium intake. Thus, investigating sex differences in responses to sodium may be important in understanding these health disparities between men and women. Central sodium sensing is critical in mediating neurohormonal responses to the relative hypernatremia associated with high salt intake. The circumventricular organs (CVOs), including the organum vasculosum lamina terminalis (OVLT) and subfornical organ (SFO), lack a complete blood brain barrier and contain osmosensitive neurons capable of sensing changes in sodium concentration in the blood. The CVOs also mediate sodium-induced changes in sympathetic nerve activity (SNA), vasopressin (AVP), thirst, and BP. Studies in humans show increased activation of the CVOs during acute hypernatremia (hypertonic saline infusion), which is similar to the underappreciated relative hypernatremia that occurs with high sodium intake. However, no human studies have investigated whether there are sex differences in central neural activation during acute hypernatremia. Therefore, the focus of this proposal is to investigate sex differences in functional connectivity of sodium sensing brain regions (SFO, OVLT) and brain regions involved in sympathetic outflow (rostral ventrolateral medulla (RVLM), nucleus tractus solitarius (NTS), caudal ventrolateral medulla (CVLM)) during acute hypernatremia (via hypertonic saline infusion) using blood oxygen level dependent (BOLD) fMRI. We will also assess whether these responses are associated with changes in AVP, norepinephrine (NE), thirst, and BP. This proposal involves 2 specific aims: aim 1 will assess sex differences in change in functional connectivity between sodium sensing brain regions (SFO, OVLT); aim 2 will assess sex differences in change in functional connectivity between sympathoregulatory brain regions (RVLM, NTS, CVLM). We hypothesize that acute hypernatremia will increase functional connectivity between sodium sensing brain regions (Aim 1) and increase connectivity with the RVLM and decrease connectivity with the NTS and CVLM (Aim 2). We hypothesize that men will have greater responses since (1) in salt sensitive rodent models, male animals display larger changes in arterial BP; (2) men have greater AVP release in response to hypertonic saline infusion; and (3) men have greater MSNA, BP, and forebrain BOLD fMRI responses to various cardiovascular stressors. This proposal has the potential to offer important insight into sex-specific mechanisms of BP regulation and fluid balance and will provide the trainee with specific instruction in BOLD fMRI and technical writing, which are critical in his development into a productive research scientist.