Translational Sciences and Experimental Medicines, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Bioscience Renal, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Ups J Med Sci. 2020 Nov;125(4):274-280. doi: 10.1080/03009734.2020.1804496. Epub 2020 Aug 19.
The most profound effect of vasopressin on the kidney is to increase water reabsorption through V-receptor (VR) stimulation, but there are also data suggesting effects on calcium transport. To address this issue, we have established an isolated perfused kidney model with accurate pressure control, to directly study the effects of VR stimulation on kidney function, isolated from systemic effects.
The role of VR in renal calcium handling was studied in isolated rat kidneys using a new pressure control system that uses a calibration curve to compensate for the internal pressure drop up to the tip of the perfusion cannula.
Kidneys subjected to VR stimulation using desmopressin (DDAVP) displayed stable osmolality and calcium reabsorption throughout the experiment, whereas kidneys not administered DDAVP exhibited a simultaneous fall in urine osmolality and calcium reabsorption. Epithelial sodium channel (ENaC) inhibition using amiloride resulted in a marked increase in potassium reabsorption along with decreased sodium reabsorption.
A stable isolated perfused kidney model with computer-controlled pressure regulation was developed, which retained key physiological functions. The preparation responds to pharmacological inhibition of ENaC channels and activation of VR. Using the model, the dynamic effects of VR stimulation on calcium handling and urine osmolality could be visualised. The study thereby provides evidence for a stimulatory role of VR in renal calcium reabsorption.
血管加压素对肾脏的最深远影响是通过 V 受体 (VR) 刺激增加水的重吸收,但也有数据表明它对钙转运有影响。为了解决这个问题,我们建立了一个具有精确压力控制的离体灌注肾脏模型,以直接研究 VR 刺激对肾脏功能的影响,从而排除系统效应的影响。
我们使用新的压力控制系统在离体大鼠肾脏中研究了 VR 在肾脏钙处理中的作用,该系统使用校准曲线来补偿直至灌注插管尖端的内部压降。
用去氨加压素 (DDAVP) 刺激 VR 的肾脏在整个实验过程中表现出稳定的渗透压和钙重吸收,而未给予 DDAVP 的肾脏则同时出现尿渗透压和钙重吸收下降。用阿米洛利抑制上皮钠通道 (ENaC) 导致钾重吸收明显增加,同时钠重吸收减少。
我们开发了一种具有计算机控制压力调节的稳定离体灌注肾脏模型,保留了关键的生理功能。该制剂对 ENaC 通道的药理学抑制和 VR 的激活有反应。使用该模型,可以直观地观察 VR 刺激对钙处理和尿渗透压的动态影响。因此,该研究为 VR 刺激在肾脏钙重吸收中的刺激作用提供了证据。