Functional impairment of renal afferent arteriolar voltage-gated calcium channels in rats with diabetes mellitus

Pamela K. Carmines, Kazuhisa Ohishi, Hideki Ikenaga

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Experiments were performed to test the hypothesis that diabetes mellitus is associated with impaired afferent arteriolar responsiveness to opening of voltage-gated calcium channels. Diabetes was induced by injection of streptozocin (65 mg/kg, i.v.) and insulin was administered via an osmotic minipump to achieve moderate hyperglycemia. Sham rats received vehicle treatments. 2 wk later, the in vitro blood-perfused juxtamedullary nephron technique was used to allow videomicroscopic measurement of afferent arteriolar contractile responses to increasing bath concentrations of either Bay K 8644 or K+. Baseline afferent arteriolar diameter in kidneys from diabetic rats (26.4±1.2 μm) exceeded that of Sham rats (19.7±1.0 μm). Bay K 8644 evoked concentration-dependent reductions in afferent diameter in both groups of kidneys; however, arterioles from Sham rats responded to 1 nM Bay K 8644 while 100 nM Bay K 8644 was required to contract arterioles from diabetic rats. The EC50 for K+-induced reductions in afferent arteriolar diameter was greater in diabetic kidneys (40±4 mM) than in kidneys from Sham rats (28±4 mM; P < 0.05). In afferent arterioles isolated by microdissection from Sham rats and loaded with fura 2, increasing bath [K+] from 5 to 40 mM evoked a 98±12 nM increase in intracellular Ca2+ concentration ([Ca2+](i)). [Ca2+](i) responses to 40 mM K+ were suppressed in afferent arterioles from diabetic rats (Δ = 63±5 nM), but were normalized by decreasing bath glucose concentration from 20 to 5 mM. These observations indicate that the early stage of insulin-dependent diabetes mellitus is associated with a functional defect in afferent arteriolar L-type calcium channels, an effect which may contribute to suppressed afferent arteriolar vasoconstrictor responsiveness and promote glomerular hyperfiltration.

Original languageEnglish (US)
Pages (from-to)2564-2571
Number of pages8
JournalJournal of Clinical Investigation
Volume98
Issue number11
DOIs
StatePublished - Dec 1 1996

Keywords

  • Bay K 8644
  • KCl
  • diltiazem
  • renal vasoconstriction
  • streptozocin

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Functional impairment of renal afferent arteriolar voltage-gated calcium channels in rats with diabetes mellitus'. Together they form a unique fingerprint.

  • Cite this