RENAL VASCULAR-RESPONSES TO HIGH AND LOW IONIZED CALCIUM - INFLUENCE OF NOREPINEPHRINE IN THE ISOLATED-PERFUSED RAT-KIDNEY

Objective and Design: The aim of this study was to examine the influen ce of norepinephrine (NE) on renal vascular responses to high (1.88 mm ol/L and low (0.56 mmol/L) perfusate-ionized calcium ([Ca2+]) in the i solated perfused kidney of the rat. High and low [Ca2+] encompassed th e clinical concentration range in this multiexperinent, randomized tri al. Materials and Methods: Rats (n = 25), ranging in age from 3 to 4 m onths, were anesthetized and the ureter and renal artery were cannulat ed. The right kidney was perfused with oxygenated, warmed albumin (67 g/L) containing Krebs-Henseleit buffer and placed in a thermostated ch amber without interruption of now. In protocol A (n = 7), steady-state high [Ca2+] (1.88 mmol/L) and low [Ca2+] (0.56 mmol/L) were institute d in randomized order in each experiment under basal conditions. In pr otocol B (n = 9), the same interventions were instituted during consta nt rate NE infusion. Changes in renal flow were measured at constant p erfusion pressure (110 mm Hg), and renal vascular resistance (RVR) was calculated, Renal function was assessed by clearance of [C-14]inulin and by fractional excretion of sodium. With NE-induced preconstriction , the increase in RVR observed during high [Ca2+] was +17.8 +/- 1.8% o f 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 decrea se in glomerular filtration rate with high [Ca2+] was not significantl y 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 cond itions), the increase in glomerular filtration rate with low [Ca2+] wa s significantly greater in the presence of NE (12 +/- 0.7 vs. 102 +/- 8.5% of control, p < 0.01). Conclusions: Whereas under basal condition s renal vascular effects of high and low [Ca2+] (varied within the cli nical concentration range) are small, the changes recorded with the sa me interventions after NE pretreatment are increased by a factor of >2 . Hypercalcemia-induced renovascular constriction and decreased functi on are unfavorable, especially in patients who are at risk for renal d ysfunction from other causes.