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


CONCLUSIONS
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.
Institute of Surgery, Department of Pharmacology, Third Military Medical University, Chongqing 400042, China.
Li
L
Kai
Zhong-feng
ZF
Wang
Yu-liang
YL
Shi
Liang-ming
LM
Liu
De-yao
DY
Hu
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002469:Cell Separation; D008638:Mesenteric Arteries / Q000166:cytology; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D012771:Shock, Hemorrhagic / Q000378:metabolism* / Q000473:pathology
D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C051844:norbinaltorphimine; D009271:Naltrexone; C024524:beta-funaltrexamine; C055382:naltrindole; D002118:Calcium