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

J. P. Tolins, L. Raij

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

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 (GRF) (0.82 vs. 1.33 ml/min, P < .01) and renal plasma flow (3.38 vs. 6.24 ml/min; P < .01) and a rise in renal vascular resistance (23.55 vs. 11.25 mm Hg·min/ml; P < .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 of 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 < .05); however, the GFR observed in the postinfusion period was significantly decreased (base line vs. final; 1.17 vs. 0.84 ml/min; P < .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.

Original languageEnglish (US)
Pages (from-to)594-599
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume245
Issue number2
StatePublished - Jan 1 1988

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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