Inhibition of myogenic autoregulation in cyclosporine nephrotoxicity in the rat

Frederick J. Kaskel, Prasad Deverajan, Aija Birzgalis, Leon C. Moore

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The mechanisms responsible for the impairment of renal blond How (RBF) autoregulation in cyclosporine nephrotoxicity were investigated with clearance and micropuncture studies in anesthetized rats. Early chronic cyclosporine nephrotoxicity (CCN) was induced in male rats by daily intramuscular injection of 10 mg/kg/day cyciosporine-A in olive oil for 7 days; control (CON) rats received vehicle injections. Glomerular filtration rate and RBF were both reduced by 33% in CCN when compared to CON rats. RBF autoregulation was also significantly impaired in CCN, with an autoregulation index (AI) of 0.53 ±0.03 vs. 0.16 + 0.01 in CON rats. Micropuncture studies showed that the tubuloglomerular feedback (TGF) system is not impaired in CCN. Rather, in CCN there was a slight resetting such that the maximun TGF response was greater and the onset occurred at lower rates of perfusion than in CON. In contrast, further micropuncture studies demonstrated that TGF-independent autoregulation of glomerular capillar pressure was significantly impaired in CCN, with an AI of 0.86 +0.09 vs. 0.57 ±0.06 in CON. These results indicate that the loss of autoregulatory ability in rats with CCN results from substantial impairment of the myogenic autoregulatory mechanism that is an intrinsic property of the preglomerular vasculature of the kidney.

Original languageEnglish (US)
Pages (from-to)250-259
Number of pages10
JournalKidney and Blood Pressure Research
Volume12
Issue number4
DOIs
StatePublished - Jan 1 1989
Externally publishedYes

Keywords

  • Blood flow
  • Glomerular capillary pressure
  • Glomerular filtration
  • Kidney
  • Tubuloglomerular feedback

ASJC Scopus subject areas

  • Nephrology
  • Cardiology and Cardiovascular Medicine

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