Advertisement

Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 324, Issue 2, pp 148–152 | Cite as

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

  • Hugo Th. Heidemann
  • John F. Gerkens
  • Edwin K. Jackson
  • Robert A. Branch
Article

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.

Key words

Amphotericin B Aminophylline Renal vasoconstriction Adenosine Angiotensin II 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Andreoli TE, Monahan M (1968) The interaction of polyene antibiotics with thin lipid membranes. J Gen Physiol 52:300–325Google Scholar
  2. Briggs JP, Wright FS (1979) Feedback control of glomerular filtration rate; Site of the effector mechanism. Am J Physiol 236:F40–47Google Scholar
  3. Butler WT, Hill GJ, Sewel CF, Knight V (1964) Amphotericin B renal toxicity in the dog. J Pharmacol Exp Ther 143:47–56Google Scholar
  4. Gerber JG, Branch RA, Nies AS, Hollifield JW, Gerkens JF (1979) Influence of hypertonic saline on canine renal blood flow and renin release. Am J Physiol 237:F441-F446Google Scholar
  5. Gerkens JF, Branch RA (1980) The influence of sodium status and furosemide on canine acute amphotericin B nephrotoxicity. J Pharmacol Exp Ther 214:306–311Google Scholar
  6. Heidemann HTH, Gerkens JF, Spickard WA, Jackson EK, Branch RA (1983) Salt repletion decreases amphotericin B induced nephrotoxiticy. Am J Med (in press)Google Scholar
  7. Osswald H, Nabakowski G, Hermes H (1980) Adenosine as a possible mediator of metabolic control of glomerular filtration rate. Int J Biochem 12:263–267Google Scholar
  8. Rhoades EG, Ginn HE, Mirchmore HG, Smith WO, Hammarsten JF (1960) Effect of amphotericin B upon renal function in man. In: Gray P, Tabenkin B, Broadley SG (eds) Antimicrobiology agents annual. Plenum Press, New York, pp 539–542Google Scholar
  9. Schnermann J (1975) Regulation of single nephron filtration rate by feedback: Facts and theories. Clin Nephrol 3:75–81Google Scholar
  10. Schnermann J, Osswald H, Hermle M (1977) Inhibitory effect of methylxanthines on feedback control of glomerular filtration rate in the rat kidney. Pflügers Arch 369:39–48Google Scholar
  11. Schnermann J, Briggs J, Wright FS (1981) Feeback-mediated reduction of glomerular filtration rate during infusion of hypertonic saline. Kid Int 20:462–468Google Scholar
  12. Spielman WS, Osswald H (1979) Blockade of postocclusive renal vasoconstriction by an angiotensin II antagonist: Evidence for an angiotensin-adenosine interaction. Am J Physiol 237:F463-F467Google Scholar
  13. Thurau K (1975) Modification of angiotensin-mediated tubuloglomerular feedback by extracellular volume. Kid Int 8:S202–207Google Scholar
  14. Wright FS, Schnermann J (1974) Interference with feedback control of glomerular filtration rate by furosemide, triflocin and cyanide. J Clin Invest 53:1695–1708Google Scholar
  15. Wright FS, Briggs JP (1977) Feedback regulation of glomerular filtration rate. Am J Physiol 233(1):F1-F7Google Scholar

Copyright information

© Springer-Verlag 1983

Authors and Affiliations

  • Hugo Th. Heidemann
    • 1
  • John F. Gerkens
    • 1
  • Edwin K. Jackson
    • 1
  • Robert A. Branch
    • 1
  1. 1.Department of Pharmacology, Division of Clinical PharmacologyVanderbilt UniversityNashvilleUSA

Personalised recommendations