Abstract
Background The most profound effect of vasopressin on the kidney is to increase water reabsorption through V2-receptor (V2R) 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 V2R stimulation on kidney function, isolated from systemic effects. Methods The role of V2R 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 V2R 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 V2R. Using the model, the dynamic effects of V2R stimulation on calcium handling and urine osmolality could be visualised. The study thereby provides evidence for a stimulatory role of V2R in renal calcium reabsorption.
Highlights
The most profound effect of vasopressin (AVP) on the kidney is to increase water reabsorption in the collecting duct mediated through vasopressin V2-receptors (V2R), but there are data that indicate effects on calcium transport (1,2)
The system was optimised by evaluating the effect of 7.5% versus 6% bovine serum albumin (BSA) in the perfusate in eight kidneys per group
The second series was performed in order to study the effect of V2R stimulation using DDAVP in six kidneys using 7.5% BSA
Summary
The most profound effect of vasopressin (AVP) on the kidney is to increase water reabsorption in the collecting duct mediated through vasopressin V2-receptors (V2R), but there are data that indicate effects on calcium transport (1,2). A pressure control system is used in many preparations in order to maintain a stable arterial pressure in the physiological range (3,7) In principle, these systems have a pressure sensor that is connected to a feedback system that regulates the perfusion pump in order to keep the pressure constant. The most profound effect of vasopressin on the kidney is to increase water reabsorption through V2-receptor (V2R) stimulation, but there are 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 V2R stimulation on kidney function, isolated from systemic effects. Methods: The role of V2R 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. The study thereby provides evidence for a stimulatory role of V2R in renal calcium reabsorption
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