Aims: 

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-b-D-ribofuranoside (AICAR).

Methods: 

Isolated preparations of mouse aorta, saphenous artery, ileum and urinary bladder were mounted for force recording at optimal length. Tissues were incubated with AICAR for 30 min. The mRNA expression of the AMPK a1 subunit was determined in samples from urinary bladder smooth muscle and aorta using quantitative real time PCR.

Results: 

AICAR produced a reversible dose-dependent relaxation in aortic rings pre-incubated with AICAR and activated with phenylephrine. Minor relaxation was noted in the other tissues. This difference in sensitivity to AICAR was not due to differences in the expression levels of AMPK a1 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.

Conclusion: 

AMPK induced relaxation of smooth muscle is tissue-specific 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.