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Adverse effect of amphotericin B administration on renal hemodynamics in the rat. Neurohumoral mechanisms and influence of calcium channel blockade

JP Tolins and L Raij

Department of Medicine, University of Minnesota, Minneapolis.

The effect of administration of amphotericin B (AMPHO) on renal hemodynamics was studied in the rat. Acute infusion (1.2 mg/kg) of AMPHO resulted in a significant fall in glomerular filtration rate (GFR) (0.82 vs. 1.33 ml/min, P less than .01) and renal plasma flow (3.38 vs. 6.24 ml/min; P less than .01) and a rise in renal vascular resistance (23.55 vs. 11.25 mm Hg.min/ml; P less than .05) compared with base-line values. Administration of AMPHO (5 mg/kg/day i.p.) for 21 days resulted in similar changes in GFR, renal plasma flow and renal vascular resistance. Pretreatment of rats with the angiotensin II receptor blocker, sar-gly angiotensin II, did not prevent the renal vasoconstriction or fall in GFR with AMPHO. Unilateral renal denervation did not prevent the decreased GFR or effective renal plasma flow after AMPHO when compared with the contralateral, innervated kidney. Pretreatment of rats with verapamil completely inhibited renal vasoconstriction during and after AMPHO. Verapamil markedly attenuated the fall in GFR observed during AMPHO (AMPHO + verapamil vs. AMPHO + vehicle; 0.73 vs. 0.26 ml/min; P less than .05); however, the GFR observed in the postinfusion period was significantly decreased (base line vs. final; 1.17 vs. 0.84 ml/min; P less than .01). The authors conclude that 1) the adverse renal hemodynamic effects of AMPHO are not directly mediated by the renin-angiotensin or renal sympathetic nervous systems and 2) pretreatment with verapamil completely prevents AMPHO- induced renal vasoconstriction.

Volume 245, Issue 2, pp. 594-599, 05/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics




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R. D. Goldman, M. Ong, J. Wolpin, J. Doyle, C. Parshuram, and G. Koren
Pharmacological Risk Factors for Amphotericin B Nephrotoxicity in Children
J. Clin. Pharmacol., August 1, 2007; 47(8): 1049 - 1054.
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Copyright © 1988 by the American Society for Pharmacology and Experimental Therapeutics.