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PH REGULATION OF ENDOGENOUS ACID PRODUCTION

内源性酸生成的 PH 调节

基本信息

批准号：
3152656
负责人：
VIRGINIA L HOOD
金额：
$ 9.23万
依托单位：
UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-08-01 至 1987-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3152656
关键词：
acid base balance acidosis acids ammonium chloride anaerobiosis bicarbonates exercise homeostasis human subject ketones lactic acidosis methionine renal failure

项目摘要

The proposed studies are designed to investigate the physiological importance and consequences of a newly described feedback regulatory system that controls acid-base homeostasis by regulating endogenous acid production. Studies will be performed in man and rats in situations where endogenous acid production is increased. The effect of acidosis (NH4Cl and methionine) and alkalosis (NaNCO3) on lactic acid production in the forearm under anerobic conditions will be tested in normal volunteers, subjects on hypocaloric ketogenic diets and patients with renal failure, to investigate whether exogenous or endogenous acid loads or retained acid can influence further endogenous acid production. The effect of acid and base loads on ketoacid production in subjects on hypocaloric ketogenic diets will be examined to evaluate the consequences of altered fat (ketone) metabolism on protein conservation and fuel utilization. This will be accomplished by measuring nitrogen balance and thermogenesis during acid-base inhibition and stimulation on ketogenesis. In chronically catheterized rats made ketotic with a Crisco diet, we will investigate the time course and reversibility of acute metabolic acidosis (HCl infusion), alkalosis (NaHCO3 infusion), chronic metabolic acidosis (CaCl2 in diet), alkalosis (chloride depleted high base diet) and acute respiratory acidosis and alkalosis on ketoacid production. As endogenous acid generation usually occurs in settings of specific energy need, eg. lactic acid during exercise and ketoacids during starvation, a regulatory mechanism independent of those needs may have widespread implications for energy utilization in physiological or pathological situations.

拟议的研究旨在调查生理一个新的反馈调节系统的重要性和后果通过调节内源性酸来控制酸碱平衡生产研究将在以下情况下在人和大鼠中进行：内源性酸产生增加。酸中毒（NH4Cl和甲硫氨酸）和碳酸氢钠（NaNCO3）对前臂乳酸产生的影响将在正常志愿者中进行测试，低热量生酮饮食和肾功能衰竭患者，以调查外源性或内源性酸负荷或保留的酸是否会影响进一步产生内源性酸。酸碱负荷对在低热量生酮饮食的受试者中，检查以评估脂肪（酮）代谢改变对蛋白质保存和燃料利用。这将通过测定酸碱抑制过程中的氮平衡和产热和刺激生酮。在长期插管的大鼠中，酮症与Crisco饮食，我们将调查的时间进程，急性代谢性酸中毒（HCl输注）、碳酸氢钠中毒（NaHCO3 输注）、慢性代谢性酸中毒（饮食中的CaCl2）、水肿（氯化物耗尽的高碱饮食）和急性呼吸性酸中毒和酮酸生产。由于内源性酸的产生通常发生在特定能量需求的设置，例如：乳酸在运动和在饥饿期间，一种独立于这些调节机制的调节机制需求可能对能源利用产生广泛影响，生理或病理情况。