Effects of pinacidil on coronary Ca(2+)-myosin phosphorylation in cold potassium cardioplegia model.
The effects of the potassium (K(+)) channel opener pinacidil (Pin) on the coronary smooth muscle Ca(2+)-myosin light chain (MLC) phosphorylation pathway under hypothermic K(+) cardioplegia were determined by use of an in vitro microvessel model. Rat coronary arterioles (100-260 microm in diameter) were subjected to 60 min of simulated hypothermic (20 degrees C) K(+) cardioplegic solutions (K(+) = 25 mM). We first characterized the time course of changes in intracellular Ca(2+) concentration, MLC phosphorylation, and diameter and observed that the K(+) cardioplegia-related vasoconstriction was associated with an activation of the Ca(2+)-MLC phosphorylation pathway. Supplementation with Pin effectively suppressed the Ca(2+) accumulation and MLC phosphorylation in a dose-dependent manner and subsequently maintained a small decrease in vasomotor tone. The ATP-sensitive K(+) (K(ATP))-channel blocker glibenclamide, but not the nitric oxide (NO) synthase inhibitor N(omega)-nitro-L-arginine methyl ester, significantly inhibited the effect of Pin. K(+) cardioplegia augments the coronary Ca(2+)-MLC pathway and results in vasoconstriction. Pin effectively prevents the activation of this pathway and maintains adequate vasorelaxation during K(+) cardioplegia through a K(ATP)-channel mechanism not coupled with the endothelium-derived NO signaling cascade.
Matsuda
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N
Division of Cardiothoracic Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Morgan
K G
KG
Sellke
F W
FW
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006324:Heart Arrest, Induced; D007036:Hypothermia, Induced; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010766:Phosphorylation / Q000187:drug effects; D020110:Pinacidil / Q000494:pharmacology*; D011188:Potassium / Q000008:administration & dosage; D026902:Potassium Channel Blockers; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018994:Myosin Light Chains; D026902:Potassium Channel Blockers; D014665:Vasodilator Agents; D020110:Pinacidil; D019001:Nitric Oxide Synthase; D011188:Potassium; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester