Opioid receptor antagonists increase [Ca2+]i in rat arterial smooth muscle cells in hemorrhagic shock.

AIM: To examine the effects of opioid receptor antagonists and norepinephrine on intracellular free Ca2+ concentration ([Ca2+]i) in mesenteric arterial (MA) smooth muscle cells (SMC) isolated from normal and hemorrhagic shocked rats in the vascular hyporesponse stage.

METHODS

The rat model of hemorrhagic shock was made by withdrawing blood to decrease the artery mean blood pressure to 3.73-4.26 kPa and keeping at the level for 3 h. [Ca2+]i of vascular smooth muscle cells (VSMC) were detected by the laser scan confocal microscopy.

RESULTS

In the hyporesponse VMSC of rats in hemorrhagic shock, selective delta-, kappa-, and mu-opioid receptor antagonists (naltrindole, nor-binaltorphimine, and beta-funaltrexamine, 100 nmol/L) as well as norepinephrine 5 micromol/L significantly increased [Ca2+]i by 47 %+/-13 %, 37 %+/-14 %, 33 %+/-10 %, and 54 %+/-17 %, respectively, although their effects were lower than those in the normal rat cells (the increased values were 148 %+/-54 %, 130 %+/-44 %, 63 %+/-17 % and 110 %+/-38 %, respectively); and the norepinephrine-induced increase in [Ca2+]i was further augmented by three delta-, kappa-, and mu-opioid receptor antagonists (50 nmol/L, respectively) application (from 52 %+/-16 % to 99 %+/-29 %, 146 %+/-54 % and 137 %+/-47 %, respectively).

CONCLUSION

The disorder of [Ca2+]i regulation induced by hemorrhagic shock was mediated by opioid receptor and alpha-adrenoceptor, which may be partly responsible for the vascular hyporesponse, and the opioid receptor antagonists improved the response of resistance arteries to vascular stimulants in decompensatory stage of hemorrhagic shock.