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Differential involvement of potassium channel subtypes in early and late sepsis-induced hyporesponsiveness to vasoconstrictors.

Abstract
This study investigated the involvement of potassium channel subtypes in the hyporesponsiveness to vasoconstrictors of an experimental model of sepsis [cecal ligation and puncture (CLP)], at 2 time points, namely, 6 and 24 hours after sepsis onset. Wistar rats were submitted to CLP or sham surgery, and 6 and 24 hours later, responses to phenylephrine were obtained before and 30 minutes after injection of potassium channel blockers. The potassium channel blockers used were tetraethylammonium (TEA; a nonselective channel blocker), glibenclamide (GLB; an adenosine triphosphate -dependent channel blocker), 4-aminopyridine (4-AP; a voltage-dependent channel blocker), apamin (APA; a small-conductance calcium-dependent channel blocker), and iberiotoxin (IBTX; a large-conductance calcium-dependent channel blocker). It was found that (1) sepsis caused a severe vascular hyporesponsiveness to phenylephrine both 6 and 24 hours after CLP, (2) TEA partially reversed the hyporesponsiveness 6 hours after CLP and completely restored vascular response to phenylephrine 24 hours after CLP, (3) apamin reversed hyporesponsiveness 6 but not 24 hours after CLP, (4) GLB restored phenylephrine response only 24 hours after CLP, and (5) IBTX and 4-AP were ineffective in all periods studied. Our results suggest that potassium channels are important effectors of sepsis-induced vascular dysfunction in vivo and that different subtypes of potassium channels are involved in early (small-conductance calcium-dependent potassium channels) and late (adenosine triphosphate -dependent potassium channels) hyporesponsiveness to vasoconstrictors caused by sepsis.
AuthorsRegina Sordi, Daniel Fernandes, Jamil Assreuy
JournalJournal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 56 Issue 2 Pg. 184-9 (Aug 2010) ISSN: 1533-4023 [Electronic] United States
PMID20505522 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Peptides
  • Potassium Channel Blockers
  • Potassium Channels
  • Vasoconstrictor Agents
  • Phenylephrine
  • Apamin
  • Tetraethylammonium
  • iberiotoxin
  • 4-Aminopyridine
  • Glyburide
Topics
  • 4-Aminopyridine (pharmacology)
  • Animals
  • Apamin (pharmacology)
  • Blood Pressure (drug effects)
  • Female
  • Glyburide (pharmacology)
  • Muscle Contraction (drug effects)
  • Muscle, Smooth, Vascular (drug effects, physiopathology)
  • Peptides (pharmacology)
  • Phenylephrine (pharmacology)
  • Potassium Channel Blockers (pharmacology)
  • Potassium Channels (physiology)
  • Rats
  • Rats, Wistar
  • Sepsis (metabolism, physiopathology)
  • Tetraethylammonium (pharmacology)
  • Time Factors
  • Vasoconstrictor Agents (pharmacology)

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