Dilation by isoflurane of preconstricted, very small arterioles from humanright atrium is mediated in part by K+-ATP channel opening

The adenosine triphosphate (ATP)-sensitive potassium channels (K+-ATP chann els) are activated by decreases in intracellular ATP and help to match broo d now to tissue needs. Such metabolism-flow coupling occurs predominantly i n the smallest arterioles measuring 50 mu m or less in diameter. Previous s tudies demonstrated that isoflurane may activate the K+-ATP channels in lar ger arteries. We examined whether isoflurane also activates the channels in the smallest arterioles of similar to 50 mu m. Microvessels of similar to 50 mu m were dissected from right atrial appendages from patients undergoin g coronary artery bypass surgery and were monitored in vitro for diameter c hanges by videomicroscopy. With or without preconstriction with the thrombo xane analog U46619 1 mu M, vessels were exposed to isoflurane 0%-3% either in the presence or absence of the K+-ATP channel blocker glibenclamide 1 mu M. Without preconstriction, isoflurane neither dilated nor constricted the vessels significantly. After preconstriction, isoflurane had a concentrati on-dependent dilation of the small arterioles (39 +/- 13% [mean +/- SD] dil ation at 3% isoflurane) (P < 0.001), and this effect was significantly atte nuated by glibenclamide (18 +/- 5% dilation at 3% isoflurane) (P < 0.01). I n comparison, nitroprusside 10(-4) M produced 79 +/- 6% dilation, and adeno sine diphosphate 10(-4) M produced 29 +/- 7% dilation. We conclude that iso flurane-mediated dilation of the smallest resistance arterioles may be in p art based on activation of the K+-ATP channels when the arterioles are rela tively constricted.