Simultaneous determination of renal plasma flow and glomerular filtration rate in conscious mice using dual bolus injection

• Introduction: The present report describes and evaluates a simple protocol for serial measurements of glomerular filtration rate (GFR) and renal plasma flow (RPF) in conscious mice. Methods: In conscious mice, a bolus of [H-3] methoxy-inulin and [C-14] para-amino-hippuric (PAH) was injected in the tail vein whereupon eight blood samples were taken during the following 75 min. Plasma concentrations were determined by liquid scintillation and clearances of the injected markers were calculated by non-compartmental pharmacokinetic data analysis of the plasma disappearance curves. In anaesthetized mice, the renal extraction ratio of PAH was determined by infusion of PAH and subsequent analysis of blood taken from the carotid artery and the renal vein. The acquired value (0.70 +/- 0.02) was used for all subsequent calculations of RPF. To evaluate the protocol, a crossover study was performed where either the vehicle or the angiotensin II AT1 receptor antagonist candesartan was given prior to the clearance measurements. Results: Baseline values of GFR and RPF were in line with those earlier reported in mice. Administration of candesartan increased RPF and reduced the filtration fraction, whereas GFR was unaltered. These changes are supported by earlier findings and demonstrate that GFR and RPF can be determined independently. Furthermore, modelling experiments demonstrated that acceptable results are obtained even if the number of blood samples is reduced to four which is a way to further simplify the procedure. Discussion: The method provides an effective way for repeated measurements of GFR and RPF in mice without potentially confounding effects of anaesthesia.

Nyckelord

Angiotensin II

AT1 receptor

Conscious

Filtration fraction

Glomerular filtration rate

Renal plasma flow

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