Effect of aminophylline on renal vasoconstriction produced by amphotericin B in the rat.
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 mumol/kg/min for 10 min followed by 0.5 mumol/kg/min) and saralasin (6 micrograms/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 less than 0.01) and 3.5 ml/min (44%, P less than 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 less than 0.05) during the 1st and 2nd amphotericin B infusions, respectively. In contrast, neither saralasin nor the direct vasodilator sodium nitroprusside (0.4-2 micrograms/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.
D000628:Aminophylline / Q000494:pharmacology*; D000666:Amphotericin B / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012077:Renal Artery / Q000187:drug effects*; D012079:Renal Circulation / Q000187:drug effects; D012504:Saralasin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D000804:Angiotensin II; D009599:Nitroprusside; D000628:Aminophylline; D000666:Amphotericin B; D012504:Saralasin