REFLEX CONTROL OF COMPENSATORY RENAL GROWTH AND FUNCTION

这项研究提案旨在提供有关 发生功能和生化变化的机制 急性单侧肾小球囊肿块减少后 肾切除(AUN)或单侧输尿管闭塞(UUO)。这些动作 影响阳离子(钠和钾)排泄的速度 对侧肾。在AUN的情况下，血流动力学信号涉及 颈动脉窦压力感受器启动阳离子反射增加 排泄，而在uuo的情况下，肾传入神经可能 负责启动对侧阳离子排泄的增加 肾脏。最近的研究表明，阿片类拮抗剂纳洛酮 防止这些动作后阳离子排泄增加。这个 拟议的研究评估内源性阿片系统在 这些反射调节是通过对动物进行AU：N和UUO来实现的 耐受硫酸吗啡的影响。更多的研究将 确定阿片受体是否参与了对这些的反应 运动存在于中枢神经系统或外周。这个 急性肾功能衰竭或输尿管梗阻后急性功能改变与 代偿性肾脏发育的启动将通过检查 这些功能肾组织的减少对血管活性的影响 大鼠对侧肾脏中鸟氨酸脱羧酶(EC 4.1.1.17)的表达 正常动物和动物都强烈地注射了纳洛酮。长期的 AUN和UUO对代偿性肥厚的影响将被确定 在阿片受体持续阻断或耐受的动物中 ODC活动受到抑制的动物。这些研究将 提供有关血容量调节的重要新信息和 钠的排泄将与改变的状态有直接关系 生理学，如高血压和病理性钠滞留 肾脏。这些研究还将深入了解导致 肾脏的代偿性生长。特别是，他们将提供新的 对循环因素作用的认识可能导致疾病的发生 功能适应与术后代偿性肥大 功能肾组织减少。

This research proposal is intended to provide new information on the mechanisms involved in the functional and biochemical changes which occur after reduction in functioning renal mass produced by acute unilateral nephrectomy (AUN) or unilateral ureteral occlusion (uuo). These maneuvers influence the rate of cation (sodium and potassium) excretion by the contralateral kidney. In the case of AUN, a hemodynamic signal involving carotid sinus baroreceptors initiates the reflex increase in cation excretion, while in the case of uuo, renal afferent nerves may be responsible for initiating increased cation excretion by the contralateral kidney. Recent studies indicate that the opiate antagonist naloxone prevents the increased cation excretion after these maneuvers. The proposed research evaluates the role of the endogenous opioid system in these reflex adjustments by carrying out AU:N and UUO in animals made tolerant to the effects of morphine sulfate. Additional studies will determine if the opiate receptor involved in the responses to these maneuvers resides in the central nervous system or in the periphery. The relationship of the acute functional changes occurring after AUN or UUO to the initiation of compensatory renal growth will be tested by examining the effect of these reductions in functioning renal tissue on activity of the enzyme ornithine decarbosylase (EC 4.1.1.17) in the contralateral kidney in normal animals and animals infused acutely with naloxone. The long-term consequences of AUN and UUO on compensatory hypertrophy will be determined in animals with continuous opiate receptor blockade or tolerance and in animals in which ODC activity has been inhibited. These studies will provide important new information on the regulation of blood volume and sodium excretion which will have direct relevance to states of altered physiology such as hypertension and the pathological retention of sodium by the kidneys. The studies will also gain insight into the mechanism leading to compensatory renal growth. In particular, they will provide new understanding on the role of circulating factors which may lead to the functional adaptation as well as the compensatory hypertrophy after reductions in functioning renal tissue.