RENAL FUNCTION IN PROTEIN DEFICIENCY

蛋白质缺乏时的肾功能

• 批准号: 3229331
• 负责人: MANUEL MARTINEZ-MALDONADO
• 金额: $ 7.59万
• 依托单位: UNIVERSITY OF PUERTO RICO MED SCIENCES
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1990-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3229331
• 关键词: adenosine monophosphate; aldosterone; angiotensins; atrial natriuretic peptide; diabetes insipidus; dietary constituent; glomerular filtration; guanosine monophosphate; hemodynamics; juxtaglomerular apparatus; kidney function; laboratory rat; norepinephrine; nutrition related tag; parathyroid hormones; prostaglandins; protein deficiency; renin

Protein malnutrition is a world wide problem. Malnutrition affects renal function, including reductions in renal plasma flow (RPF) and glomerular filtration rate (GFR). We have also found reduced peripheral renin (PRA) and aldosterone activity, resistance to the hypertensive effects of exogenous norepinephrine (NE) and increased sensitivity to the blood pressure-lowering effects of alpha blockade. The mechanisms involved in these changes remain largely unknown. The specific aim of this proposal is to establish the role played by various hormones and substances in this condition. Our data indicate that reduced the production of vasodilator prostaglandins and, possibly, increased sensitivity to the vasoconstrictor effects of angiotensin II and norepinephrine may be partly responsible for the reduced RPF, GFR and PRA. Also, low protein feeding of rats led to a fall in immunoreactive parathyroid hormone (iPTH), that may have curtailed the fall in GFR. We propose experiments to systematically examine the role of renin, angiotensin prostaglandins, NE, atrial natriuretic factor (ANF), antidiuretic hormone (ADH), and PTH on systemic and renal hemodynamics. Experiments will be conducted in rats fed low protein (6% casein) for two or sixteen weeks compared to controls pair-fed isocaloric normal protein (23% casein) diet. Balance, clearance and micropuncture studies (Munich-Wistar) will be done in intact, diabetes insipidus (Brattleboro) and parathyroidectomized rats. In addition, experiments will be conducted in isolated glomeruli and juxtaglomerular (granular) cells to determine the role of cyclic nucleotides (AMP and GMP), prostaglandins and various pharmacological agents in renin release. Radiocalcium fluxes and pharmacological manipulation of intracellular Ca mobilization will be performed in these preparations to determine the role of Ca. These experiments should provide important information regarding the systemic and renal hemodynamic changes associated with experimental and, possibly, human protein deficiency.

蛋白质营养不良是一个世界性的问题。营养不良影响 肾功能，包括肾血浆流量(RPF)和 肾小球滤过率(GFR)。我们还发现减少了 外周肾素(PRA)和醛固酮活性，抵抗 外源性去甲肾上腺素(NE)的降压作用及升压作用 对阿尔法降压作用的敏感性 封锁。这些变化所涉及的机制在很大程度上仍然存在 未知。这项建议的具体目的是建立 各种激素和物质在这种情况下所起的作用。 我们的数据表明，血管扩张剂的产生减少 前列腺素，并可能增加对 血管紧张素II和去甲肾上腺素的血管收缩作用 对RPF、GFR和PRA的减少负有部分责任。另外，低 蛋白质喂养导致大鼠甲状旁腺免疫反应性下降 激素(IPTH)，这可能减少了GFR的下降。我们 建议进行实验，系统研究肾素的作用， 血管紧张素前列腺素、去甲肾上腺素、心钠素 抗利尿激素(ADH)和甲状旁腺素对全身和肾脏的影响 血流动力学。实验将在喂低饲料的大鼠身上进行 与对照组相比，添加蛋白质(6%酪蛋白)2周或16周 配对喂养等卡路里正常蛋白(23%酪蛋白)日粮。平衡， 将进行清除和显微穿刺法研究(慕尼黑-维斯塔尔) 在完整的，尿崩症(Brattleboro)和 去甲状旁腺大鼠。此外，实验将是 在孤立的肾小球和肾小球旁(颗粒状)进行 以确定环核苷酸(AMP和GMP)的作用， 前列腺素和各种药物在肾素释放中的作用。 放射性钙离子通量与药物调控 在这些细胞中进行细胞内钙动员 为确定钙的作用做准备。这些实验应该 提供有关全身和肾脏的重要信息 与实验相关的血流动力学变化，可能， 人类蛋白质缺乏症。