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.