Document Detail

Exaggerated impact of ATP-sensitive K(+) channels on afferent arteriolar diameter in diabetes mellitus.
MedLine Citation:
PMID:  10864575     Owner:  NLM     Status:  MEDLINE    
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 microm) than in sham rats (20.8 +/- 1.0 microm). Glibenclamide (3 to 300 microM) 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 microm (P > 0.05 versus sham baseline). In both groups of rats, pinacidil (a cyanoguanidine K(ATP) agonist; 0.3 to 300 microM) 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 gliben-clamide-sensitive afferent arteriolar dilator response to 1 microM 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.
H Ikenaga; J P Bast; R W Fallet; P K Carmines
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of the American Society of Nephrology : JASN     Volume:  11     ISSN:  1046-6673     ISO Abbreviation:  J. Am. Soc. Nephrol.     Publication Date:  2000 Jul 
Date Detail:
Created Date:  2000-07-27     Completed Date:  2000-07-27     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  9013836     Medline TA:  J Am Soc Nephrol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1199-207     Citation Subset:  IM    
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MeSH Terms
Adenosine Triphosphate / pharmacology*
Arterioles / drug effects,  physiopathology*
Benzopyrans / pharmacology
Cyclopentanes / pharmacology
Diabetes Mellitus, Experimental / physiopathology*
Diabetes Mellitus, Type 1 / physiopathology
Glyburide / pharmacology
Hypoglycemic Agents / pharmacology
Pinacidil / pharmacology
Potassium Channel Blockers
Potassium Channels / drug effects*,  physiology*
Rats, Sprague-Dawley
Vasodilator Agents / pharmacology
Vasomotor System / drug effects,  physiopathology
Grant Support
Reg. No./Substance:
0/Benzopyrans; 0/Cyclopentanes; 0/Hypoglycemic Agents; 0/Potassium Channel Blockers; 0/Potassium Channels; 0/Vasodilator Agents; 121055-10-5/SDZ PCO 400; 7B0ZZH8P2W/Pinacidil; 8L70Q75FXE/Adenosine Triphosphate; SX6K58TVWC/Glyburide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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