Nadeau Louis, Arbour Danielle, Mouginot Didier
Centre de Recherche du CHUQ CHUL, Neurosciences and Université Laval, Québec G1V 4G2, Canada.
BMC Physiol. 2010 Aug 25;10:17. doi: 10.1186/1472-6793-10-17.
In mammals, vasopressin (AVP) is released from magnocellular neurons of the hypothalamus when osmotic pressure exceeds a fixed set-point. AVP participates to the hydromineral homeostasis (HH) by controlling water excretion at the level of the kidneys. Our current understanding of the HH and AVP secretion is the result of a vast amount of data collected over the five past decades. This experimental data was collected using a number of systems under different conditions, giving a fragmented view of the components involved in HH.
Here, we present a high-level model of the rat HH based on selected published results to predict short-term (hours) to long-term (days) variation of six major homeostatic parameters: (1) the extracellular sodium concentration, (2) the AVP concentration, (3) the intracellular volume, (4) the extracellular volume, (5) the urine volume and (6) the water intake. The simulation generates quantitative predictions like the daily mean of the extracellular sodium concentration (142.2 mmol/L), the AVP concentration, (1.7 pg/ml), the intracellular volume (45.3 ml/100 g body weight--bw), the extracellular volume (22.6 ml/100 g bw), the urine volume (11.8 ml/100 g bw) and the cumulative water intake (18 ml/100 g bw). The simulation also computes the dynamics of all these parameters with a high temporal resolution of one minute. This high resolution predicts the circadian fluctuation of the AVP secretion (5 ± 2 pg/ml) and defines the limits of a restoration and a maintenance phase in the HH (2.1 pg/ml). Moreover, the simulation can predict the action of pharmacological compounds that disrupt the HH. As an example, we tested the action of a diuretic (furosemide) combined with a sodium deficient diet to generate quantitative prediction on the extracellular sodium concentration (134 mmol/L) and the need-induced water intake (20.3 ml/100 g bw). These simulated data are compatible with experimental data (136 ± 3 mmol/L and 17.5 ± 3.5 ml/100 g bw, respectively).
The quantitative agreement of the predictions with published experimental data indicates that our simplified model of the HH integrates most of the essential systems to predict realistic physiological values and dynamics under a set of normal and perturbed hydromineral conditions.
在哺乳动物中，当渗透压超过固定设定点时，下丘脑的大细胞神经元会释放血管加压素（AVP）。AVP通过控制肾脏水平的水排泄参与水盐稳态（HH）。我们目前对HH和AVP分泌的理解是过去五十年来收集的大量数据的结果。这些实验数据是在不同条件下使用多种系统收集的，对HH中涉及的成分给出了零散的认识。
在此，我们基于选定的已发表结果提出大鼠HH的高级模型，以预测六个主要稳态参数的短期（数小时）至长期（数天）变化：（1）细胞外钠浓度，（2）AVP浓度，（3）细胞内体积，（4）细胞外体积，（5）尿量和（6）水摄入量。模拟产生定量预测，如细胞外钠浓度的每日平均值（142.2 mmol/L）、AVP浓度（1.7 pg/ml）、细胞内体积（45.3 ml/100 g体重——bw）、细胞外体积（22.6 ml/100 g bw）、尿量（11.8 ml/100 g bw）和累积水摄入量（18 ml/100 g bw）。模拟还以一分钟的高时间分辨率计算所有这些参数的动态变化。这种高分辨率预测了AVP分泌的昼夜波动（5±2 pg/ml），并定义了HH中恢复和维持阶段的界限（2.1 pg/ml）。此外，模拟可以预测破坏HH的药理化合物的作用。例如，我们测试了利尿剂（呋塞米）与缺钠饮食联合使用的作用，以对细胞外钠浓度（134 mmol/L）和需求诱导的水摄入量（20.3 ml/100 g bw）产生定量预测。这些模拟数据与实验数据（分别为136±3 mmol/L和17.5±3.5 ml/100 g bw）相符。
预测结果与已发表实验数据的定量一致性表明，我们简化的HH模型整合了大多数基本系统，以预测在一组正常和受干扰的水盐条件下的实际生理值和动态变化。
