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Regulation of Endothelial-Dependent Relaxation in Human Systemic Arteries by SK_Ca and IK_Ca Channels

Maternal and Fetal Health Research Centre, Division of Human Development, St Mary's Hospital, Manchester, United Kingdom

J. E. Myers, PhD

Maternal and Fetal Health Research Centre, Division of Human Development, St Mary's Hospital, Manchester, United Kingdom; Maternal & Fetal Health Research Centre, University of Manchester, St Mary's Hospital, Hathersage Road, Manchester M13 0JH, UK; jenny.myers{at}manchester.ac.uk

P. N. Baker, MD

Maternal and Fetal Health Research Centre, Division of Human Development, St Mary's Hospital, Manchester, United Kingdom

M. J. Taggart, PhD

Maternal and Fetal Health Research Centre, Division of Human Development, St Mary's Hospital, Manchester, United Kingdom; Smooth Muscle Physiology Group, Division of Cardiovascular and Endocrine Sciences, University of Manchester, United Kingdom

Blockade of small-conductance Ca ²⁺-activated K⁺ channels (SK_Ca) and intermediate conductance Ca²⁺-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_CaK⁺ 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).

Key Words: SKCa channels • IKCa channels • vasodilatation • human arteries • EDHF

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