Impaired myogenic responsiveness of the afferent arteriole in streptozotocin-induced diabetic rats: Role of eicosanoid derangements

Koichi Hayashi, Murray Epstein, Rodger Loutzenhiser, Haytey Forster

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Abstract

Evidence suggests that diabetes is associated with an impairment of renal autoregulation. It has previously been demonstrated that pressure-induced (myogenic) afferent arteriolar vasoconstriction is well preserved in the isolated perfused hydronephrotic kidney. In this study, pressure-induced afferent arteriolar vasoconstriction was examined in kidneys from sfreptozotocin-induced diabetic rats. Vessel diameters were measured by videomicroscopy as renal arterial pressure was elevated from 80 to 180 mm Hg. In normal kidneys, the afferent arteriole vasoconstricted progressively as renal arterial pressure was increased (-24 ± 2% decrement in diameter at 180 mm Hg; N = 35; P < 0.001). In contrast, afferent arterioles of diabetic kidneys exhibited a greatly attenuated response to pressure (i.e., -3 ± 2% change at 180 mm Hg; N = 60). In vitro treatment wilh 100 μM ibuprofen completely restored myogenic vasoconstriction (-21 ± 2% change at 180 mm Hg), but did not alter myogenic responses of control (i.e., nondiabetic) kidneys. The control of hyperglycemie by insulin treatment resulted in a partial preservation of myogenic vasoconstriction (i.e., -11 ± 3% change at 180 mm Hg), which was further restored by the administration of a low dose (10 μM) of ibuprofen (-21 ± 1% change at 180 mm Hg). These observations indicate that diabetes is associated with an impaired responsiveness of the afferent arteriole to pressure that is mediated by an alteration in eicosanoid metabolism. This deranged renal microcirculatory response to pressure may represent a functional impairment of the diabetic kidney that may contribute to the progression of diabetic nephropathy.

Original languageEnglish
Pages (from-to)1578-1586
Number of pages9
JournalJournal of the American Society of Nephrology
Volume2
Issue number11
Publication statusPublished - 1992 May 1

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Keywords

  • Afferent arteriole
  • Diabetes mellitus
  • Myogenic vasoconstriction
  • Prostaglandins
  • Renal autoregulation

ASJC Scopus subject areas

  • Nephrology

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