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 与血压(BP)相关的疾病仍然是两性公共卫生的主要挑战。男人有一种 与60岁左右的女性相比，高血压的患病率更高，60岁以后的患病率更高 这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 与饮食中高钠摄入量有关。因此，研究对钠的反应的性别差异可能 了解男性和女性之间的这些健康差距很重要。中枢钠感应是 在调节与高盐摄入相关的相对高钠血症的神经激素反应方面至关重要。这个 室周器官(CVO)，包括终板血管器和穹隆下 器官(SFO)，缺乏完整的血脑屏障，含有能够感知变化的渗透敏感神经元 血液中的钠浓度。CVOS还介导钠引起的交感神经变化。 活动(SNA)、加压素(AVP)、口渴和血压。对人类的研究表明，CVO的激活增加 在急性高钠血症(高渗盐水输注)期间，这类似于被低估的亲属 高钠血症与高钠摄入有关的高钠血症。然而，还没有人体研究调查是否有 急性高钠血症时中枢神经活动的性别差异。因此，这项提案的重点是 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(延髓头端腹外侧区、孤束核 (NTS)，尾侧延髓腹外侧部(CVLM)在急性高钠血症时(通过高渗盐水输注)，使用 血氧水平依赖(BOLD)功能磁共振成像。我们还将评估这些反应是否与 AVP、去甲肾上腺素、口渴和血压的变化。该提案涉及两个具体目标：目标1将评估 钠敏感脑区之间功能连接变化的性别差异(SFO，OVLT)；目标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 钠感应脑区(目标1)，增加与RVLM的连通性，减少与 NTS和CVLM(目标2)。我们假设男性会有更大的反应，因为(1)对盐敏感 啮齿动物模型，雄性动物表现出更大的动脉血压变化；(2)男性有更大的AVP释放作为反应 (3)男性对高渗盐水输注有更大的MSNA、BP和前脑FMRI反应。 各种心血管应激源。这项提议有可能对性别差异提供重要的见解。 血压调节和液体平衡的机制，并将为学员提供具体的粗体指导 功能磁共振成像和技术写作，这对他成为一名多产的研究科学家至关重要。