Tempol prevents altered K+ channel regulation of afferent arteriolar tone in diabetic rat kidney

Carmen M. Troncoso Brindeiro, Pascale H. Lane, Pamela K. Carmines

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Experiments were performed to test the hypothesis that oxidative stress underlies the enhanced tonic dilator impact of inward-rectifier K channels on renal afferent arterioles of rats with streptozotocin-induced diabetes mellitus. Sham and diabetic rats were left untreated or provided Tempol in their drinking water for 26±1 days, after which afferent arteriolar lumen diameter and its responsiveness to K channel blockade were measured using the in vitro blood-perfused juxtamedullary nephron technique. Afferent diameter averaged 19.4±0.8 μm in sham rats and 24.4±0.8 μm in diabetic rats (P<0.05). The decrease in diameter evoked by Ba (inward-rectifier K channel blocker) was 3 times greater in diabetic rats than in sham rats. Glibenclamide (KATP channel blocker) and tertiapin-Q (Kir1.1/Kir3.x channel blocker) decreased afferent diameter in diabetic rats but had no effect on arterioles from sham rats. Chronic Tempol treatment prevented diabetes mellitus-induced increases in both renal vascular dihydroethidium staining and baseline afferent arteriolar diameter. Moreover, Tempol prevented the exaggeration of afferent arteriolar responses to Ba, tertiapin-Q, and glibenclamide otherwise evident in diabetic rats. Preglomerular microvascular smooth muscle cells expressed mRNA encoding Kir1.1, Kir2.1, and Kir6.1. Neither diabetes mellitus nor Tempol altered Kir1.1, Kir2.1, Kir6.1, or SUR2B protein levels in renal cortical microvessels. To the extent that the effects of Tempol reflect its antioxidant actions, our observations indicate that oxidative stress contributes to the exaggerated impact of Kir1.1, Kir2.1, and KATP channels on afferent arteriolar tone during diabetes mellitus and that this phenomenon involves posttranslational modulation of channel function.

Original languageEnglish (US)
Pages (from-to)657-664
Number of pages8
Issue number3
StatePublished - Mar 2012


  • ATP-sensitive K channels
  • ROMK
  • Tempol
  • diabetes mellitus
  • inward-rectifier K channels

ASJC Scopus subject areas

  • Internal Medicine


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