Opioid Receptor Antagonists Modulate Ca2+-activated K+ Channels in Mesenteric Arterial Smooth Muscle Cells of Rats in Hemorrhagic Shock

Previous study has indicated a significant enhancement of activity of large-conductance Ca 2+ -activated K + channel (BK Ca ) in mesenteric arterial vascular smooth muscle cells isolated from rats in vascular hyporesponsive stage of hemorrhagic shock. In the present study, the effect of opioid receptor antagonism on BK Ca activity in the vascular smooth muscle cells of rats in the hyporesponse stage of hemorrhagic shock was investigated by using inside-out configuration of the patch-clamp technique. The results showed that naloxone (10 μM) down-regulated the activity of BK Ca by reducing open probability (P o ) and open frequency of the channels. The reduction of P o resulted from a decrease of mean open time and an increase of the slow closed time constant. Naltrindole and nor-binaltorphimine (100 nM) had the similar effects to that of naloxone, but no significant effect of β-funaltrexamine (100 nM) on the activity of the channels could be found. These results suggest that δ- and K-opioid receptors, but not μ-receptors, may be involved in the regulation of BK Ca in vascular hyporesponse stage, and that inhibition of BK Ca may be one of the mechanisms of the opioid receptor antagonists improving the response of resistance arteries to vasoactive stimulants during the decompensatory stage of hemorrhagic shock.