Renal function in mice: effects of volume expansion and angiotensin II

The present study was performed to validate a simple means for assessing renal function in anesthetized mice and to characterize the renal hemodynamic responses to acute volume expansion and how these responses are altered by concurrent angiotensin II (AngII) infusions. Inulin and para-aminohippurate clearances were used to assess GFR and renal plasma flow (RPF) in three groups of male C57Bl/6 mice anesthetized with inactin (100 mg/kg, intraperitoneally) and ketamine (10 mg/kg). To avoid the hypotension associated with repeated blood sampling, a single blood sample was taken after three timed urine collections. Renal function and mean arterial pressure (MAP) were measured under euvolemic conditions (2.5 microl/min, intravenously, n = 7) during isotonic saline volume expansion (12.5 microl/min, intravenously, n = 5) and during volume expansion with concurrent AngII infusion (5 ng/min x g, n = 5). MAP in the control group was 77 +/- 2 mmHg; volume expansion alone did not change MAP significantly (83 +/- 2 mmHg), but led to significantly greater values in both GFR and RPF (1.35 +/- 0.14 versus 1.01 +/- 0.1 ml/min x g and 11.26 +/- 1.39 versus 6.29 +/- 0.5 ml/min x g, respectively). Infusion of AngII during volume expansion led to significant elevations of MAP (100 +/- 3 mmHg, P < 0.05) and prevented the increases in GFR and RPF elicited by volume expansion (0.77 +/- 0.08 and 5.35 +/- 0.48 ml/min x g, respectively). Volume expansion also elicited marked increases in absolute and fractional sodium excretion (6.1 +/- 1.0 versus 0.62 +/- 0.2 microEq/min x g and 3.1 +/- 0.7 versus 0.4 +/- 0.1%, respectively). AngII infusion attenuated the absolute and fractional sodium excretion responses to volume expansion (3.4 +/- 1.2 microEq/min x g and 2.5 +/- 0.5%, respectively). The present findings demonstrate that anesthetized mice exhibit marked renal hemodynamic and excretory responses to isotonic saline volume expansion. Concomitant AngII infusion attenuates these responses in spite of greater increases in arterial pressure.