Calcium-activated potassium channels contribute to human skeletal muscle microvascular endothelial dysfunction related to cardiopulmonary bypass

• Published in: Surgery 2008-08, Vol.144 (2), p.239-244
• Main Authors: Liu, Yuhong, MD, Sellke, Eric W, Feng, Jun, MD, PhD, Clements, Richard T., PhD, Sodha, Neel R., MD, Khabbaz, Kamal R., MD, Senthilnathan, Venkatachalam, MD, Alper, Seth L., MD, PhD, Sellke, Frank W., MD
• Format: Article
• Language: English
• Subjects: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology; Aged; Apamin - pharmacology; Benzimidazoles - pharmacology; Biological and medical sciences; Cardiopulmonary Bypass - adverse effects; Dose-Response Relationship, Drug; Endothelium, Vascular - metabolism; Endothelium, Vascular - physiopathology; Female; General aspects; Humans; In Vitro Techniques; Indoles - pharmacology; Intermediate-Conductance Calcium-Activated Potassium Channels - metabolism; Large-Conductance Calcium-Activated Potassium Channels - metabolism; Male; Medical sciences; Muscle, Skeletal - blood supply; Oximes - pharmacology; Peptides - pharmacology; Potassium Channels; Potassium Channels, Calcium-Activated - metabolism; Pyrazoles - pharmacology; Small-Conductance Calcium-Activated Potassium Channels - metabolism; Surgery; Vasoconstrictor Agents; Vasodilation
• ISSN: 0039-6060; 1532-7361
• DOI: 10.1016/j.surg.2008.03.032

Background We investigated the role of calcium-activated potassium (KCa ) channel activity in human skeletal muscle microvascular function in the setting of cardiopulmonary bypass (CPB). Methods and Results Human skeletal muscle arterioles (80- to 180 μm 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 KCa channel activators/blockers and several other vasodilators. Post-CPB responses to the activator of intermediate (IKCa ) and small conductance (SKCa ) KCa 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 (BKCa ) KCa 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 BKCa , IKCa , and SK3Ca were not altered post-CPB. Conclusion 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.