Accumulation of acidic renin isoforms in kidneys of cyclosporine-A-treated rats

Laura L. Norling, Alda Tufro-McReddie, R. Ariel Gomez, Leon C. Moore, Frederick J. Kaskel

Research output: Contribution to journalArticle

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Abstract

Chronic cyclosporin A (CsA) treatment results in major hemodynamic changes in the renal microvasculature and in expression of the intrarenal renin angiotensin system. Changes in renin expression in kidneys of CsA-treated rats include the recruitment of immunoreactive renin in afferent arterioles and in the juxtaglomerular apparatus. This study presents evidence that an acidic isoform of renin is increased in kidneys of CsA-treated rats. Immunoblots of rat kidney homogenate separated by polyacrylamide-gel electrophoresis and also by isoelectric focusing demonstrate the presence of an acidic isoform (pI 5.5 and estimated molecular weight of approximately 32 to 36 kd) seen in increased amounts in kidney homogenate from CsA-treated rats. Silver-stained two-dimensional gels of renin separated from kidney homogenate with pepstatin agarose confirm the presence of an acidic renin isoform in CsA-treated rats. In rats that received CsA for varied intervals of 1, 3, 5, and 8 wk, this acidic isoform is shown to significantly accumulate relative to duration of treatment with CsA when immunoreactive bands are analyzed by densitometric scanning (r2 = 0.90, P < 0.001). Renin enzymatic activity also increased in kidney homogenate of CsA-treated rats relative to duration of treatment with CsA (r2 = 0.486, P < 0.001). Prorenin in these same samples was significantly decreased compared with controls. The acidic renin isoform identified in kidney homogenate of CsA-treated rats may be involved in the vascular changes that are seen in this model.

Original languageEnglish (US)
Pages (from-to)331-337
Number of pages7
JournalJournal of the American Society of Nephrology
Volume7
Issue number2
StatePublished - Feb 1996
Externally publishedYes

Fingerprint

Renin
Cyclosporine
Protein Isoforms
Kidney
Juxtaglomerular Apparatus
Isoelectric Focusing
Arterioles
Renin-Angiotensin System
Microvessels
Silver
Sepharose
Blood Vessels
Polyacrylamide Gel Electrophoresis
Molecular Weight
Hemodynamics
Gels

Keywords

  • Arteriolopathy
  • Nephrotoxicity
  • Prorenin
  • Renin processing

ASJC Scopus subject areas

  • Nephrology

Cite this

Accumulation of acidic renin isoforms in kidneys of cyclosporine-A-treated rats. / Norling, Laura L.; Tufro-McReddie, Alda; Gomez, R. Ariel; Moore, Leon C.; Kaskel, Frederick J.

In: Journal of the American Society of Nephrology, Vol. 7, No. 2, 02.1996, p. 331-337.

Research output: Contribution to journalArticle

Norling, LL, Tufro-McReddie, A, Gomez, RA, Moore, LC & Kaskel, FJ 1996, 'Accumulation of acidic renin isoforms in kidneys of cyclosporine-A-treated rats', Journal of the American Society of Nephrology, vol. 7, no. 2, pp. 331-337.
Norling, Laura L. ; Tufro-McReddie, Alda ; Gomez, R. Ariel ; Moore, Leon C. ; Kaskel, Frederick J. / Accumulation of acidic renin isoforms in kidneys of cyclosporine-A-treated rats. In: Journal of the American Society of Nephrology. 1996 ; Vol. 7, No. 2. pp. 331-337.
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