Electrolyte handling in the isolated perfused rat kidney: demonstration of vasopressin V2-receptor-dependent calcium reabsorption

Abstract

Background: The most profound effect of vasopressin on the kidney is to increase water reabsorption through V 2-receptor (V 2 R) 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 V 2 R stimulation on kidney function, isolated from systemic effects. Methods: The role of V 2 R 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. Results: Kidneys subjected to V 2 R 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. Conclusions: 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 V 2 R. Using the model, the dynamic effects of V 2 R stimulation on calcium handling and urine osmolality could be visualised. The study thereby provides evidence for a stimulatory role of V 2 R in renal calcium reabsorption.