ns-309 and iberiotoxin

We investigated the role of calcium-activated potassium (K(Ca)) channel activity in human skeletal muscle microvascular function in the setting of cardiopulmonary bypass (CPB).. Human skeletal muscle arterioles (80- to 180 microm in diameter) were dissected from tissue harvested before and after CPB. In vitro relaxation responses of precontracted arterioles in a pressurized no-flow state were examined in the presence of K(Ca) channel activators/blockers and several other vasodilators. Post-CPB responses to the activator of intermediate (IK(Ca)) and small conductance (SK(Ca)) K(Ca) channels, NS309, to the endothelium-dependent vasodilator adenosine 5'-diphosphate (ADP), and to substance P were reduced compared with pre-CPB responses (P < .05), respectively, whereas responses to the activator of large conductance (BK(Ca)) K(Ca) channels, NS1619, and to the endothelium-independent vasodilator, sodium nitroprusside (SNP) were unchanged. Endothelial denudation decreased NS309-induced relaxation and abolished that induced by ADP or substance P (P < .05), but had no effect on relaxation induced by either NS1619 or SNP. Polypeptide levels of BK(Ca), IK(Ca), and SK3(Ca) were not altered post-CPB.. IK/SK-mediated relaxation is predominantly endothelium dependent, whereas BK-mediated relaxation seems to be largely independent of endothelial function in human skeletal muscle microvasculature. CPB-associated microvascular dysfunction likely arises in part from impaired function of endothelial SK and IK channels in the peripheral microvasculature.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Aged; Apamin; Benzimidazoles; Cardiopulmonary Bypass; Dose-Response Relationship, Drug; Endothelium, Vascular; Female; Humans; In Vitro Techniques; Indoles; Intermediate-Conductance Calcium-Activated Potassium Channels; Large-Conductance Calcium-Activated Potassium Channels; Male; Muscle, Skeletal; Oximes; Peptides; Potassium Channels; Potassium Channels, Calcium-Activated; Pyrazoles; Small-Conductance Calcium-Activated Potassium Channels; Vasoconstrictor Agents; Vasodilation