Abstract
Perindopril, a new specific and potent inhibitor of angiotensin-I-converting enzyme, was used to evaluate the possible participation of inhibition of the renin-angiotensin system in the development of aminoglycoside-induced renal failure. Kidney function, morphology and biochemistry were evaluated at regular intervals throughout the study. Perindopril was given orally to rats at a daily dose of 2 mg/kg for 15 days prior to and during 15-day gentamicin treatment given intraperitoneally at a daily dose of 50 mg/kg. Perindopril treatment alone induced no modification in renal function or structure. Gentamicin treatment alone induced typical renal lesions which were scored as moderate and a slight but significant decrease in ACE blood levels. Concurrent treatment with perindopril and gentamicin induced a greater drop in ACE blood levels than after the administration of perindopril alone and produced more marked renal impairment than after the administration of gentamicin alone. These observations suggest that the integrity of the renin-angiotensin system may play an important role in limiting kidney injury during aminoglycoside-induced nephrotoxicity.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Barrett AJ (1976) An improved color reagent for use in Barrett's assay of cathepsin B. Anal Biochem 76: 374
Baylis C, Rennke HR, Brenner BM (1977) Mechanisation of the defect in glomerular ultrafiltration associated with gentamicin administration. Kidney Int 12: 344
Bennett JV, Brodie JL, Benner EJ, Kirby WMM (1966) Simplified, accurate method for antibiotic assay of clinical specimens. Appl Microbiol 14: 170
Bennett WM (1983) Aminoglycoside nephrotoxicity. Nephron 35: 73
Bennett WM, Hartnett MN, Gilbert D, Houghton D, Porter GA (1976) Effect of sodium intake on gentamicin nephrotoxicity in the rat. Proc Soc Exp Biol Med 151: 736
Brinker K, Cronin R, Bulger R, Southern P, Henrich W (1979) Potassium depletion: risk factor for and consequence of gentamicin nephrotoxicity. Clin Res 27: 764A
Brunner HR, Waeber B, Nussberger J (1987) Angiotensin converting enzyme and the kidney. Kidney Int 31: s104
Carlier MB, Laurent P, Claes PJ, Vanderhaeghe H, Tulkens PM (1983) Inhibition of lysosomal phospholipases by aminoglycoside antibiotics: in vitro comparative studies. Antimicrob Agents Chemother 23: 440
Chahwala SB, Harpur ES (1983) Gentamicin induced hypercalciuria in the rat. Acta Pharmacol Toxicol 53: 358
Cushman DW, Cheung HS (1971) Spectrophotometric assay and properties of the angiotensin converting enzyme of rabbit lung. Biochem Pharmacol 20: 1637
De Broe ME, Paulus GJ, Verpooten GA, Roels F, Buyssens N, Wedeen R, Van Hoof F, Tulkens PM (1984) Early effects of gentamicin, tobramycin, and amikacin on the human kidney. Kidney Int 25: 643
Drummer OH, Kourtis S (1987) Biotransformation studies of diacid angiotensin converting enzyme inhibitors. Arzneim Forschung 37: 1225
Feldman S, Wang M, Kaloyanides GJ (1982) Aminoglycosides induce a phospholipidosis in the renal cortex of the rat: an early manifestation of nephrotoxicity. J Pharmacol Exp Ther 220: 514
Fruncillo RJ, Rocci ML, Vlasses PH, Mojaverian P, Shepley K, Clementi RA, Oren A, Smith RD, Till AE, Riley LJ, Krishna G, Narins RG, Ferguson RK (1987) Disposition of enalapril and enalaprilat in renal insufficiency. Kidney Int 31(S20): 117
Gal AE, Brady RO, Hibbert SR, Pentchev PG (1975) A practical chromogenic procedure for the detection of homozygotes and heterozygous carriers of Niemann-Pick disease. N Engl J Med 293: 632
Gilbert DN, Houghton DC, Bennett WM, Plamp CE, Reger K, Porter GA (1979) Reversibility of gentamicin nephrotoxicity in rats: recovery during continued administration. Proc Soc Exp Biol Med 160: 99
Gilman A (1970) A protein binding assay for adenosine -3′-5′-cyclic monophosphate. Proc Natl Acad Sci USA 67: 305
Haylor J, Lote CJ (1980) Renal function in conscious rats after indomethacin: evidence of a tubular action of endogenous prostaglandins. J Physiol 298: 298
Higa EMS, Schor N, Boim MA, Atzen H, Ramos OL (1981) Role of the prostaglandin and kallikrein kinin systems in aminoglycoside-induced acute renal failure. Braz J Med Biol Res 18: 355
Hjelle JT, Morin JP, Trouet A (1981) Analytical cell fractionation of isolated rabbit renal proximal tubules. Kidney Int 20: 71
Humes HD, Sastrasinh M, Weinberg JM (1984) Calcium is a competitive inhibitor of gentamicin-renal membrane binding interactions and dietary calcium supplementation protects against gentamicin nephrotoxicity. 73: 134
Kaloyanides GJ, Pastoriza-Munoz E (1980) Aminoglycoside nephrotoxicity. Kidney Int 18: 571
Kimbrough HM, Vaughan ED, Carey MN, Ayer S (1977) Effect of intrarenal angiotensin II blockade on renal function in conscious dogs. Circ Res 40: 174
Klotman PE, Boatman JE, Volpp BD, Baker JD, Yarger WE (1985) Captopril enhances aminoglycoside nephrotoxicity in potassium-depleted rats. Kidney Int 28: 118
Laubie M, Schiavi P, Vincent M, Scmitt H (1984) Inhibition of angiotensin I converting enzyme with S-9470. Biochemical effects, interspecies differences and role of sodium diet in hemodynamic effects. J Cardiovasc Pharmacol 6: 1076
Laurent G, Carlier MB, Rollman B, Van Hoof F, Tulkens PM (1982) Mechanism of aminoglycoside induced lysosomal phospholipidosis in vitro and in vivo studies with gentamicin and amikacin. Biochem Pharmacol 31: 3861
Le Treut A, Couliou H, Delabary M, Larzul JJ, Delabarthe B, Le Gall JY (1979) Le dosage de l'enzyme de conversion de l'antiogensine I par méthode spectrophotométrique. Clin Chim Acta 98: 1
Luft FC, Rankin LJ, Sloan RS, Yum MN (1978) Recovery from aminoglycoside nephrotoxicity with continued-drug administration. Antimicrob Agents Chemother 14: 284
Luft FC, Aronoff GR, Evan AP, Connors BA, Weinberg MH, Kleit SA (1982) The renin angiotensin system in aminoglycoside induced acute renal failure. J Pharmacol Exp Ther 220: 427
Marche P, Olier B, Girard A, Fillastre JP, Morin JP (1987) Aminoglycoside-induced alterations of phosphoinositide metabolism. Kidney Int 31: 59
Mimram A, Casellas D (1987) The renin-angiotensin system and nephron function heterogeneity. Kidney Int 31 S20: 57
Morin JP, Viotte G, Vandewalle A, Van Hoof F, Tulkens P, Fillastre JP (1980) Gentamicin induced nephrotoxicity: a cell biology approach. Kidney Int 18: 583
Morin JP, Olier B, Viotte G, Grancher G, Grancher G, Paumier JC (1984) The lysosomal toxicity of aminoglycosides: a morphometric approach. Int J Tiss React 6: 427
Olier B, Morin JP, Grancher G, Fillastre JP (1987) Regenerating tubular cell process in rat kidney: influence of gentamicin treatment. Int J Tiss React 9: 241
Plummer DT, Noorazar S, Haslam JD (1982) The effect of gentamicin and coenzyme Q on the excretion of enzymes and ions in rat urine. In: Fillastre JP (ed) Nephrotoxicity ototoxicity of drugs. Colloque INSERM, Université de Rouen, pp 178–194
Pugh D, Leaback EA, Walker PG (1957) Studies on glucosaminidases: N-acetyl-β-d-glucosaminidase in rat kidney. Biochem J 65: 464
Schor N, Ichikawa I, Rennke HG, Troy JL (1981) Pathophysiology of altered glomerular function in aminoglycoside-treatment. Kidney Int 19: 288
Terragno NA, Terragno DA, McGiff JC (1977) Contribution of prostaglandins to the renal circulation in concious, anesthetized and laparotomized dogs. Circ Res 40: 590
Toubeau G, Laurent G, Carlier MB, Abid S, Maldague P, Heuson-Stiennon JA, Tulkens P (1986) Tissue repair in rat kidney cortex after short treatment with aminoglycosides at low doses. A comparative biochemical and morphometric study.
Tulkens PM, de Broe ME, Maldague P, Heuson-Stiennon JA (1984) Lysosomal alterations in aminoglycoside induced acute renal failure. Kidney Dis Series 4: 299
Unger T, Moursi M, Ganten D, Herman K, Lang RE (1987) Antihypertensive action of the converting enzyme inhibitor perindopril (S 9490-3) in spontaneously hypertensive rats comparison with enalapril (MK 421) and ramipril (HOE 498). J Cardiovasc Pharmacol 8: 276
Wheiton A (1982) Renal tubular transport and intrarenal aminoglycoside distribution. In: Whelton A, Neu HC (eds) microbiology, clinical use and toxicology. p 191
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Morin, J.P., Thomas, N., Toutain, H. et al. Modulation of gentamicin nephrotoxicity by chronic inhibition of angiotensin-I-converting enzyme in rat. Arch Toxicol 63, 47–53 (1989). https://doi.org/10.1007/BF00334634
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00334634