ALTERATIONS IN RENAL PROSTAGLANDINS IN AGING

衰老过程中肾前列腺素的变化

• 批准号: 3745514
• 负责人: BARBARA A CLARK
• 金额: --
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3745514
• 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.

内源性前列腺素的生物合成强烈影响肾功能。 我们的初步研究表明，肾脏产生的前列腺素 (特别是PGE2)随着年龄的增长而逐渐受损。这 肾功能缺陷可能与某些肾功能紊乱有关。 与衰老相关的，包括排泄水分和 刺激肾素和醛固酮的分泌。常见病 老年人(特别是老年妇女)等由噻嗪诱发 因此，低钠血症和低肾素性低醛固酮血症可能有关。 前列腺素新陈代谢。我们将通过研究来检验这一假设 健康的青年、中老年受试者以及体弱多病的老年人 这些疾病的病史。所有研究都将在女性中进行，以 避免尿前列腺素被前列腺液污染。 前列腺素E_2排泄对生理/药物刺激的反应 如水利尿、不饱和脂肪酸饮食挑战和 将检查激氨酸酶抑制及其对肾功能的影响 注意到了。抑制前列腺素合成的平行研究， 使用消炎痛，也将进行。同时测量的 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产生，因为 这些因素相互作用，对肾脏和血管系统产生影响。 结果应该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 并提出预防和治疗的方法。