Summary
Administration of the antifungal agent amphotericin B causes a pronounced reduction in renal blood flow (RBF). Since amphotericin B induced renal vasoconstriction may contribute to the clinical nephrotoxicity of this drug, the purpose of these studies was to investigate the mechanism of amphotericin B induced renal vasoconstriction. To determine if the vascular response to amphotericin B is linked to the intrarenal release of either adenosine or angiotensin II, the effects of aminophylline (5 μmol/kg/min for 10 min followed by 0.5 μmol/kg/min) and saralasin (6 μg/min) on the renal vascular response produced by two 10 min intravenous amphotericin B (0.35 mg/kg) infusions were examined. In the control group, amphotericin B decreased RBF 1.7 ml/min (22%, P<0.01) and 3.5 ml/min (44%, P<0.001) during the 1st and 2nd amphotericin B infusions, respectively. In animals pretreated with aminophylline the decrease in RBF produced by amphotericin B was only 0.4 ml/min (5.5%; N.S.) and 1.3 ml/min (15%, P<0.05) during the 1st and 2nd amphotericin B infusions, respectively. In contrast, neither saralasin nor the direct vasodilator sodium nitroprusside (0.4–2 μg/min) influenced the renal vascular response to amphotericin B. These data suggest that the renal vascular response to amphotericin B is not linked to the formation of angiotensin II, but rather might be mediated by increases in renal adenosine levels.
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This work was supported by Grants GM 15431 and HL 14192. H. Heidemann was supported by a grant from Deutsche Forschungsgemeinschaft. E. Jackson was a recipient of a Pharmaceutical Manufacturers Association Faculty Development Award in Pharmacology
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Heidemann, H.T., Gerkens, J.F., Jackson, E.K. et al. Effect of aminophylline on renal vasoconstriction produced by amphotericin B in the rat. Naunyn-Schmiedeberg's Arch. Pharmacol. 324, 148–152 (1983). https://doi.org/10.1007/BF00497021
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DOI: https://doi.org/10.1007/BF00497021