PMID- 18713554
OWN - NLM
STAT- MEDLINE
DCOM- 20081126
LR  - 20131121
IS  - 0366-6999 (Print)
IS  - 0366-6999 (Linking)
VI  - 121
IP  - 14
DP  - 2008 Jul 20
TI  - Anti-apoptotic effect of morphine-induced delayed preconditioning on pulmonary 
      artery endothelial cells with anoxia/reoxygenation injury.
PG  - 1313-8
AB  - BACKGROUND: Opioid preconditioning (PC) reduces anoxia/reoxygenation (A/R) injury 
      to various cells. However, it remains unclear whether opioid-induced delayed PC 
      would show anti-apoptotic effects on pulmonary artery endothelial cells (PAECs) 
      suffering from A/R injury. The present study was conducted to elucidate this 
      issue and to investigate the potential mechanism of opioid-induced delayed PC. 
      METHODS: Cultured porcine PAECs underwent 16-hour anoxia followed by 1-hour 
      reoxygenation 24 hours after pretreatment with saline (NaCl; 0.9%) or morphine (1 
      micromol/L). To determine the underlying mechanism, a non-selective K(ATP) 
      channel inhibitor glibenclamide (Glib; 10 micromol/L), a nitric oxide (NO) 
      synthase blocker NG-nitro-L-arginine methyl ester (L-NAME; 100 micromol/L), and 
      an opioid receptor antagonist naloxone (Nal; 10 micromol/L) were given 30 minutes 
      before the A/R load. The percentage of apoptotic cells was assessed by terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. 
      eNOS mRNA level was measured by real-time polymerase chain reaction (PCR). NO 
      content of PAECs supernatants was measured with the Griess reagent. RESULTS: 
      Compared to the A/R PAECs, morphine-induced delayed PC significantly reduced 
      PAECs apoptosis ((18.1 +/- 1.9)% vs (5.5 +/- 0.3)%; P < 0.05), increased NO 
      release ((11.4 +/- 1.3) micromol/L vs (20.5 +/- 2.1) micromol/L, P < 0.05), and 
      up-regulated eNOS gene expression nearly 9 times (P < 0.05). The anti-apoptosis 
      effect of morphine was abolished by pretreatment with Glib, L-NAME and Nal, but 
      the three agent-selves did not aggravate the A/R injury. Furthermore, L-NAME and 
      Nal offset the enhanced release of NO caused by pretreatment with morphine. 
      CONCLUSIONS: Morphine-induced delayed PC prevents A/R injury of PAECs. This 
      effect may be mediated by activation of K(ATP) channel via opioid receptor and NO 
      signaling pathways.
FAU - Ding, Wen-gang
AU  - Ding WG
AD  - Department of Anesthesiology, Second Hospital of Harbin Medical University, 
      Harbin, Heilongjiang 150086, China.
FAU - Zhou, Hua-cheng
AU  - Zhou HC
FAU - Cui, Xiao-guang
AU  - Cui XG
FAU - Li, Wen-zhi
AU  - Li WZ
FAU - Guo, Yue-ping
AU  - Guo YP
FAU - Zhang, Bing
AU  - Zhang B
FAU - Liu, Wei
AU  - Liu W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Narcotic Antagonists)
RN  - 0 (RNA, Messenger)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 36B82AMQ7N (Naloxone)
RN  - 76I7G6D29C (Morphine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - S88TT14065 (Oxygen)
RN  - SX6K58TVWC (Glyburide)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Analgesics, Opioid/pharmacology
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Cell Hypoxia
MH  - Cells, Cultured
MH  - Endothelial Cells/cytology/*drug effects/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Glyburide/pharmacology
MH  - In Situ Nick-End Labeling
MH  - Morphine/*pharmacology
MH  - NG-Nitroarginine Methyl Ester/pharmacology
MH  - Naloxone/pharmacology
MH  - Narcotic Antagonists/pharmacology
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type III/antagonists & inhibitors/genetics/metabolism
MH  - Oxygen/*pharmacology
MH  - Pulmonary Artery/cytology
MH  - RNA, Messenger/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Swine
EDAT- 2008/08/21 09:00
MHDA- 2008/12/17 09:00
CRDT- 2008/08/21 09:00
PHST- 2008/08/21 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/08/21 09:00 [entrez]
PST - ppublish
SO  - Chin Med J (Engl). 2008 Jul 20;121(14):1313-8.