Sex Differences in Central Neural Activation During Acute Hypernatremia

急性高钠血症期间中枢神经激活的性别差异

• 批准号: 10749516
• 负责人: Nathan Romberger
• 金额: $ 4.29万
• 依托单位: UNIVERSITY OF DELAWARE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10749516
• 关键词: Acute; Adult; Age; Androgen Receptor; Animals; Blood; Blood - brain barrier anatomy; Blood Pressure; Brain; Brain region; Cardiac Output; Cardiovascular system; Catecholamines; Cell Nucleus; Data; Dehydration; Development; Dietary Sodium; Disease; Estrogen Receptors; Event; Exercise; Fluid Balance; Functional Magnetic Resonance Imaging; Goals; Gonadal Steroid Hormones; Head; High Prevalence; Hormonal; Human; Hypernatremia; Hypertension; Hypothalamic structure; Incidence; Infusion procedures; Instruction; Insula of Reil; Intake; Ischemia; Isometric Exercise; Lower Body Negative Pressure; Measures; Mediating; Menstrual cycle; Muscle; Nerve; Neurons; Norepinephrine; Organ; Peripheral Resistance; Phase; Plasma; Prevalence; Productivity; Prosencephalon; Public Health; Research; Rest; Rodent; Rodent Model; Saline; Scientist; Sex Differences; Signal Transduction; Sodium; Sodium Chloride; Subfornical Organ; Thirst; Training; Vasopressins; Woman; Women' s Role; blood oxygen level dependent; blood pressure control; blood pressure regulation; cardioprotection; female sex hormone; health disparity; insight; male; men; neural; neuroimaging; neuroregulation; organum vasculosum of the lamina terminalis; response; salt intake; salt sensitive; sex; stressor; technical writing; young woman

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.

项目摘要/摘要 在两性中，血压（BP）相关疾病仍然是一个主要的公共卫生挑战。男人有一个 与女性相比，高血压的患病率更高，直到60岁左右，此后患病率更高 女性，反映了女性性激素的心脏保护作用。成人高血压的高发病率 与高饮食钠摄入量有关。因此，研究对钠反应的性别差异可能 对于了解男女之间的健康差异很重要。中央钠感应是 对与高盐摄入相关的相对高钠血症的神经激素反应至关重要。这 弯曲的器官（CVO），包括lamina lamina末端（OVLT）​​和亚叶片 器官（SFO）缺乏完整的血脑屏障，并且含有能够传感变化的渗透敏感神经元 在血液中的钠浓度中。 CVO还介导钠引起的交感神经变化 活性（SNA），加压素（AVP），口渴和BP。人类研究表明，CVO的激活增加 在急性高钠血症（高渗盐水输注）期间，这类似于相似的相对相对 高钠摄入量发生的高钠血症。但是，没有人类研究调查是否存在 急性高钠血症期间中枢神经激活的性别差异。因此，该提议的重点 是为了研究钠感应大脑区域（SFO，OVLT）​​和 涉及交感神经流出的大脑区域（Rostral腹外侧髓质（RVLM），核Tractus solitarius （NTS），急性高钠血症期间（通过高渗盐水输注），尾腔外侧髓质（CVLM）） 血氧水平依赖（BOLD）fMRI。我们还将评估这些响应是否与 AVP，去甲肾上腺素（NE），口渴和BP的变化。该建议涉及2个具体目标：AIM 1将评估 钠感应大脑区域之间功能连通性变化的性别差异（SFO，OVLT）​​；目标2 将评估交感调节大脑区域之间功能连通性变化的性别差异 （RVLM，NTS，CVLM）。我们假设急性高钠血症将增加功能连接性 钠感应大脑区域（AIM 1）并提高与RVLM的连通性，并降低与 NTS和CVLM（AIM 2）。我们假设男性在（1）对盐敏感以来的反应会更大 啮齿动物模型，雄性动物在动脉BP中显示出更大的变化。 （2）男性的AVP释放更大 输注高渗盐水； （3）男性具有更大的MSNA，BP和前脑BOLD FMRI对 各种心血管应激源。该提议有可能对特定于性别的重要见解 BP调节和流体平衡的机制，将为受训者提供粗体的特定指导 fMRI和技术写作，这对于他发展成为一名生产研究科学家至关重要。