Effects of pinacidil on coronary Ca-myosin phosphorylation in cold potassium cardioplegia model

Matsuda, Naruto, Kathleen G. Morgan, and Frank W. Sellke. Effects of pinacidil on coronary Ca-myosin phosphorylation in cold potassium cardioplegia model. Am J Physiol Heart Circ Physiol 279: H882–H888, 2000.—The effects of the potassium (K) channel opener pinacidil (Pin) on the coronary smooth muscle Ca-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 mm in diameter) were subjected to 60 min of simulated hypothermic (20°C) K cardioplegic solutions (K 5 25 mM). We first characterized the time course of changes in intracellular Ca concentration, MLC phosphorylation, and diameter and observed that the K cardioplegia-related vasoconstriction was associated with an activation of the Ca-MLC phosphorylation pathway. Supplementation with Pin effectively suppressed the Ca accumulation and MLC phosphorylation in a dosedependent manner and subsequently maintained a small decrease in vasomotor tone. The ATP-sensitive K (KATP)channel blocker glibenclamide, but not the nitric oxide (NO) synthase inhibitor N-nitro-L-arginine methyl ester, significantly inhibited the effect of Pin. K cardioplegia augments the coronary Ca-MLC pathway and results in vasoconstriction. Pin effectively prevents the activation of this pathway and maintains adequate vasorelaxation during K cardioplegia through a KATP-channel mechanism not coupled with the endothelium-derived NO signaling cascade.