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.