Regulation of endothelial-dependent relaxation in human systemic arteries by SKCa and IKCa channels.
Blockade of small-conductance Ca (2)(+)-activated K(+) channels (SK(Ca)) and intermediate conductance Ca(2)(+)-activated K(+) channels (IK(Ca)) can cause inhibition of endothelium-dependent hyperpolarizing factor (EDHF) in many vascular beds from animals, but there is a relative paucity of data in human vessels. Systemic arteries, isolated from women with healthy pregnancies, relax to the endothelial-dependent agonist bradykinin via a nonprostacyclin and non-nitric oxide pathway attributable to EDHF. Therefore, in this study, the authors investigated the effect of pharmacological blockade of SK(Ca) and IK(Ca) on EDHF-mediated relaxation of human omental and myometrial arteries preconstricted with either arginine vasopressin or U46619. Human arteries were isolated from omental and myometrial biopsies taken from healthy women undergoing planned cesarean section at term. Endothelial function was assessed using wire myography. In all vessels examined, nonspecific blockade of IK(Ca) with charybdotoxin attenuated EDHF-attributed relaxation. However, when Tram 34 was used to block IK(Ca), the attenuation of relaxation was evident only with U46619 preconstriction. In arteries from both vascular beds, and with either preconstrictor, a combination of either apamin and charybdotoxin or apamin plus Tram 34 almost ablated EDHF-attributable relaxation. These data support the notion that in human systemic arteries, activation of, primarily, SK(Ca) and IK(Ca)K(+) channel subtypes underlies EDHF-mediated relaxation. These results have important implications for future studies ascertaining the molecular mechanisms of hypertensive disorders (eg, preeclampsia, in which EDHF is thought to be aberrant).
Gillham
J C
JC
Maternal and Fetal Health Research Centre, Division of Human Development, St Mary's Hospital, Manchester, United Kingdom.
Myers
J E
JE
Baker
P N
PN
Taggart
M J
MJ
D001158:Arteries / Q000502:physiology*; D002585:Cesarean Section; D018999:Charybdotoxin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects / Q000502:physiology*; D008969:Molecular Sequence Data; D009215:Myometrium / Q000098:blood supply; D009852:Omentum / Q000098:blood supply; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology*; D011247:Pregnancy; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496923:KCNN4 protein, human; D024681:Potassium Channels, Calcium-Activated; D018999:Charybdotoxin