OBJECTIVE AND DESIGN: The aim of this study was to examine the influence of norepinephrine (NE) on renal vascular responses to high (1.88 mmol/L) and low (0.56 mmol/L) perfusate-ionized calcium ([Ca2+]) in the isolated perfused kidney of the rat. High and low [Ca2+] encompassed the clinical concentration range in this multiexperiment, randomized trial. MATERIALS AND METHODS: Rats (n = 25), ranging in age from 3 to 4 months, were anesthetized and the ureter and renal artery were cannulated. The right kidney was perfused with oxygenated, warmed albumin (67 g/L) containing Krebs-Henseleit buffer and placed in a thermostated chamber without interruption of flow. In protocol A (n = 7), steady-state high [Ca2+] (1.88 mmol/L) and low [Ca2+] (0.56 mmol/L) were instituted in randomized order in each experiment under basal conditions. In protocol B (n = 9), the same interventions were instituted during constant rate NE infusion. Changes in renal flow were measured at constant perfusion pressure (110 mm Hg), and renal vascular resistance (RVR) was calculated. Renal function was assessed by clearance of [14C]inulin and by fractional excretion of sodium. With NE-induced preconstriction, the increase in RVR observed during high [Ca2+] was +17.8 +/- 1.8% of control, and the decrease in RVR observed during low [Ca2+] was -35.9 +/- 8.2% of control. Both values were greater by a factor of 2 than corresponding results obtained under basal conditions (7 +/- 2.1% vs. -13.5 +/- 4.1% of control, respectively, p < 0.05). Whereas the decrease in glomerular filtration rate with high [Ca2+] was not significantly influenced by NE pretreatment (-9 +/- 1.8% of control with high [Ca2+] in combination with NE vs. 4.1 +/- 0.7% of control under basal conditions), the increase in glomerular filtration rate with low [Ca2+] was significantly greater in the presence of NE (12 +/- 0.7 vs. 102 +/- 8.5% of control, p < 0.01). CONCLUSIONS: Whereas under basal conditions renal vascular effects of high and low [Ca2+] (varied within the clinical concentration range) are small, the changes recorded with the same interventions after NE pretreatment are increased by a factor of > 2. Hypercalcemia-induced renovascular constriction and decreased function are unfavorable, especially in patients who are at risk for renal dysfunction from other causes.