The Role of Potassium Channels in Sirolimus-induced Vascular Effects on Human Arteries
ProQuest, 2008 - 160 pages
Our third objective was to show that sirolimus causes an increase in the outward potassium current via the direct activation of the KATP. Our findings indicate that specific KATP currents were recorded from the human coronary artery smooth muscle cells and provide direct evidence that sirolimus causes an opening of the KATP channels in these cells. The data generated demonstrate the important role played by sirolimus on KATP channels in maintaining the vasomotor tone of human radial arteries and human coronary arteries. This study has important clinical applications as sirolimus-eluting stents are used to maintain patency of vessel grafts post coronary artery bypass surgery. Our findings may aid in developing and designing a more effective drug-eluting stent.
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CHARACTERIZATION OF THE RESPONSES
SIROLIMUS INDUCES ENDOTHELIUM
IMMUNOLOCALIZATION OF KATp CHANNEL
STUDY OF THE EFFECT OF SIROLIMUS ON
2A subunit acetylcholine action of sirolimus aprikalim artery smooth muscle blocking peptide calcium causes relaxation concentrations of sirolimus contracted with U46619 coronary artery bypass coronary artery smooth cumulative addition currents of human diltiazem Donkey Anti drug drug-eluting stent effect of sirolimus eluting stents endothelium endothelium-dependent Figure FITC glibenclamide glyburide human arteries human coronary artery human radial artery iberiotoxin indomethacin ion channels isolated human radial KATP channels KATP channels current KAtp subunits Kir 6.2 subunits Log concentration-response curves mechanisms of vasorelaxation membrane potential muscle cell actin optimal tension organ chamber outward potassium current patch clamp PE-Cy5 dye pharmacological agents phenylephrine point represents potassium channels primary antibodies protein Radial arterial rings relaxation of isolated relaxation response Representative micrograph represents the mean response to sirolimus role sirolimus causes sirolimus-eluting stent Sirolimus-induced relaxation smooth muscle cells smooth muscle layer studies Sur 2A vascular smooth muscle vasodilation vasomotor tone vasorelaxation vessel graft