期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 695, 期 1-3, 页码 88-95出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2012.07.025
关键词
AICAR; AMPK; Mouse; PKC; NO; SNP
资金
- Swedish Research Council
- Karolinska Institutet
- FP7 EU grant (INComb)
- Swedish Heart-Lung Foundation
Adenosine monophosphate activated kinase (AMPK), a regulator of cellular metabolism, has been shown to relax arterial smooth muscle via endothelium-dependent and independent mechanisms. We have examined the role of AMPK in different smooth muscles using the activating compound, 5-amino-4-imidazolecarboxamide riboside-1-beta-ribofuranoside (AICAR). Isolated preparations of mouse aorta, saphenous artery, ileum and urinary bladder were compared. AICAR produced a reversible dose-dependent relaxation in aortic rings pre-incubated with AICAR and activated with phenylephrine. Less prominent relaxation was noted in the other tissues. This difference in sensitivity to AICAR was not due to differences in the expression levels of AMPK alpha 1 mRNA. In the aorta, AICAR had a greater effect on contractions induced by phenylephrine, compared to high-K+ induced contractions. Contractions of the aorta in response to the protein kinase C activator PDBu were prominently inhibited by AICAR. The AICAR relaxation observed in the aorta was not prevented by the NOS inhibitor L-NAME, Indomethacin or endothelium removal. Nitric oxide (NO) mediated relaxations in aortic preparations induced by acetylcholine or sodium nitroprusside (SNP) were attenuated by AICAR. In conclusion, AMPK induced relaxation of smooth muscle is tissue-dependent and most prominent in large elastic arteries. The smooth muscle relaxation is NO-independent and occurs downstream of PKC activation and is associated with attenuated relaxant responses to NO. (C) 2012 Elsevier B.V. All rights reserved.
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