Effect of aminophylline on renal vasoconstriction produced by amphotericin B in the rat

Abstract

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%, PPP<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.