Differential involvement of potassium channel subtypes in early and late sepsis-induced hyporesponsiveness to vasoconstrictors.
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.
Sordi
Regina
R
Department of Pharmacology, Universidade Federal de Santa Catarina, SC, Brazil.
Fernandes
Daniel
D
Assreuy
Jamil
J
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000503:physiopathology; D010455:Peptides / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000378:metabolism / Q000503:physiopathology*; D019789:Tetraethylammonium / Q000494:pharmacology; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D001030:Apamin; D019789:Tetraethylammonium; C064719:iberiotoxin; D015761:4-Aminopyridine; D005905:Glyburide