ALTERATIONS IN RENAL PROSTAGLANDINS IN AGING

衰老过程中肾前列腺素的变化

• 批准号: 6097844
• 负责人: BARBARA A CLARK
• 金额: --
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-01 至 1999-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6097844
• 关键词: acute renal failure; aging; aldosterone; arginine vasopressin; atrial natriuretic peptide; blood chemistry; captopril; cardiovascular function; creatinine; dietary supplements; diuresis; eicosanoid metabolism; electrolytes; endothelin; female; hormone regulation /control mechanism; human middle age (35-64); human old age (65+); human subject; hyponatremia; hyporeninemic hypoaldosteronism; indomethacin; inulin; kidney function; kidney metabolism; nutrition related tag; prostaglandin E; renin; steroid hormone metabolism; thiazide; urinalysis; young adult human (21-34)

Endogenous prostaglandin biosynthesis powerfully influences renal function. Our preliminary studies indicate that renal production of prostaglandins (specifically PGE2) is progressively impaired with advancing age. This deficiency may be implicated in certain disturbances in renal function associated with aging, including an impaired ability to excrete water and to stimulate the secretion of renin and aldosterone. Common disorders of the elderly (especially elderly women) such as thiazide-induced hyponatremia and hyporeninemic hypoaldosteronism might therefore be related to prostaglandin metabolism. We will test this hypothesis by studying healthy young, middle-aged and old subjects as well as infirm elderly with a history of these disorders. All studies will be carried out in women to avoid contamination of urinary prostaglandins with prostatic secretions. The response of PGE2 excretion to physiological/pharmacological stimuli such as water diuresis, dietary challenge with unsaturated fatty acids and kininase inhibition will be examined and the effects on renal function noted. Parallel studies of the inhibition of prostaglandin synthesis, using indomethacin, will also be performed. Simultaneous measurements of the plasma levels of atrial natriuretic peptide, arginine vasopressin, renin/aldosterone, and endothelin will be made in many experiments, since these factors interact in their effects on the kidney and vascular system. The results should provide information about renal prostaglandin metabolism and its relationship to renal function in the elderly, clarify the pathophysiology of electrolyte disorders to which aged patients are predisposed, and suggest approaches to their prevention and therapy.

内源性前列腺素生物合成强烈影响肾功能。 我们的初步研究表明，肾脏产生的泽兰素， 前列腺素E2（特别是PGE 2）随着年龄的增长而逐渐受损。 这 缺乏可能与某些肾功能紊乱有关 与衰老有关，包括排泄水的能力受损， 以刺激肾素和醛固酮的分泌。 常见疾病 老年人（特别是老年妇女），如噻嗪诱导 因此，低钠血症和低肾素性低醛固酮症可能相关 前列腺素代谢。 我们将通过研究 健康的青年、中年和老年受试者以及 这些疾病的病史。 所有研究都将在女性中进行， 避免前列腺分泌物污染尿前列腺素。 PGE_2分泌对生理/药理刺激的反应 例如水利尿、不饱和脂肪酸饮食挑战， 将检查激肽酶抑制和对肾功能的影响 知道了 前列腺素合成抑制的平行研究， 使用吲哚美辛，也将进行。 同时测量 血浆心钠素，精氨酸加压素， 肾素/醛固酮和内皮素将在许多实验中制备，因为 这些因素相互作用，对肾脏和血管系统产生影响。 结果应提供有关肾脏前列腺素代谢的信息 及其与老年人肾功能的关系，阐明 老年患者电解质紊乱的病理生理学 易患病，并提出预防和治疗方法。