NEURAL CONTROL OF RENAL FUNCTION IN HYPERTENSION

这项拟议的研究旨在检查生理和 肾功能神经调控的病理生理学意义 高血压。环境和遗传因素如何相互作用， 交感神经系统的活动和肾脏的变化 功能有助于发展、维护和加剧 高血压将通过两种主要方式进行调查：1)检查 环境应激对动脉的急性影响机制 清醒高血压大鼠的血压控制机制(脑、肾) 模型；以及2)检查这些机制在 慢性暴露所致高血压的发病机制 环境压力。在这些研究中，将使用环境压力 作为一种生理刺激来激活意识中的交感神经流出 老鼠。具体目标1将决定α或β肾上腺素能受体 杏仁中央核内介导的肾交感神经兴奋 急性接触铅引起的神经活动和抗心绞痛 清醒自发性高血压患者的环境应激(空气应激) 老鼠。具体目标#2将检查增强的肾脏交感神经 自发性高血压患者对空气应激的神经活动和抗心钠素反应 高钠摄入的高血压大鼠通过中枢神经调节 系统α-2肾上腺素能受体。肾血管和肾小管是否 高钠摄入的自发性高血压大鼠对 肾交感神经活动比自发的增加 对正常钠摄入量的高血压大鼠也将进行检查。特定的 目标3解决环境压力是否增加的问题 肾交感神经活动与减少尿钠排泄 其他清醒高血压大鼠模型，即DOCA-SALT、DAHL 盐敏感型和交界型(SHR×WKY)高血压大鼠。 具体目标#4将检查长期暴露在环境中 应激引起或加重清醒大鼠的高血压 肾脏交感神经活动，从而增强肾脏钠离子滞留。 具体目标#5将检查高钠饮食是否会加速 慢性暴露所致高血压的发生或发展 通过进一步增强肾交感神经对抗环境应激 活动性和肾脏钠滞留。

The proposed research is designed to examine the physiological and pathophysiological significance of the neural control of renal function in hypertension. How the interaction of environmental and genetic factors, activity of the sympathetic nervous system, and alterations in renal function contribute to the development, maintenance, and exacerbation of hypertension will be investigated in two main ways: 1) examining mechanisms of the acute effects of environmental stress on arterial pressure control mechanisms (brain, kidneys) in conscious hypertensive rat models; and 2) examining the importance of these mechanisms in the pathogenesis of hypertension resulting from exposure to chronic environmental stress. In these studies, environmental stress will be used as a physiological stimulus to activate sympathetic outflow in conscious rats. Specific Aim #1 will determine whether alpha- or beta-adrenoceptors in the central amygdaloid nucleus mediate the increased renal sympathetic nerve activity and antinatriuresis resulting from acute exposure to environmental stress (air stress) in conscious spontaneously hypertensive rats. Specific Aim #2 will examine whether the enhanced renal sympathetic nerve activity and antinatriuretic responses to air stress in spontaneously hypertensive rats on high sodium intake are mediated via central nervous system alpha-2 adrenoceptors. Whether the renal vasculature and tubules of spontaneously hypertensive rats on high sodium intake are more sensitive to increases in renal sympathetic nerve activity than spontaneously hypertensive rats on normal sodium intake will also be examined. Specific Aim #3 addresses the question of whether environmental stress increases renal sympathetic nerve activity and decreases urinary sodium excretion in other conscious hypertensive rat models, i.e., DOCA-salt, Dahl salt-sensitive, and borderline (crossbred SHR x WKY) hypertensive rats. Specific Aim #4 will examine whether chronic exposure to environmental stress produces or exacerbates hypertension in conscious rats by increasing renal sympathetic nerve activity, thus enhancing renal sodium retention. Specific Aim #5 will examine whether high sodium diet accelerates the development or progression of hypertension resulting from chronic exposure to environmental stress by further enhancing renal sympathetic nerve activity and renal sodium retention.