Exaggerated impact of ATP-sensitive K+ channels on afferent arteriolar diameter in diabetes mellitus

Hideki Ikenaga, Joseph P. Bast, Rachel W. Fallet, Pamela K. Carmines

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Abstract

Experiments were performed to determine the involvement of ATP-sensitive K+ channels (K(ATP) channels) in the renal afferent arteriolar dilation that occurs during the hyperfiltration stage of insulin-dependent diabetes mellitus (IDDM). IDDM was induced in rats by streptozotocin (STZ) injection, and adequate insulin was provided to maintain moderate hyperglycemia. Sham rats received vehicle treatments. Two weeks later, afferent arteriolar function was assessed using the in vitro blood-perfused juxtamedullary nephron technique. Baseline afferent arteriolar lumen diameter was greater in STZ rats (25.9 ± 1.1 μm) than in sham rats (20.8 ± 1.0 μm). Glibenclamide (3 to 300 μM) had virtually no effect on afferent arterioles from sham rats; however, this K(ATP) antagonist caused concentration-dependent afferent arteriolar constriction in kidneys from STZ-treated rats, restoring lumen diameter to 20.6 ± 1.7 μm (P > 0.05 versus sham baseline). In both groups of rats, pinacidil (a cyanoguanidine K(ATP) agonist; 0.3 to 300 μM) evoked concentration-dependent afferent arteriolar dilation, indicating the functional expression of K(ATP) channels; however, lumen diameter was increased by 73% in STZ kidneys but only by 48% in sham kidneys: The glibenclamide-sensitive afferent arteriolar dilator response to 1 μM PCO-400 (a benzopyran K(ATP) agonist) was also accentuated in STZ kidneys. These observations suggest that increases in both the functional availability and basal activation of K(ATP) channels promote afferent arteriolar vasodilation during the early stage of IDDM, changes that likely contribute to the etiology of diabetic hyperfiltration.

Original languageEnglish (US)
Pages (from-to)1199-1207
Number of pages9
JournalJournal of the American Society of Nephrology
Volume11
Issue number7
StatePublished - Jul 1 2000

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ASJC Scopus subject areas

  • Nephrology

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