title: Role of AMP-activated protein kinase in α-lipoic acid-induced vasodilatation in spontaneously hypertensive rats.
abstract: BACKGROUND
  Adenosine monophosphate (AMP)-activated protein kinase (AMPK) has recently emerged as an attractive and novel target for the regulation of vascular smooth muscle contraction. The present study investigated the vasodilatory effects of α-lipoic acid (α-LA) and the possible mechanism of its action on aortic rings from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR).
  
  
  METHODS
  Aortae were removed from WKY and SHR, and contractile responses to acetylcholine and α-LA studied in organ chamber. Phosphorylated AMPK (pAMPK), phosphorylated Peutz-Jeghers syndrome kinase LKB1 (pLKB1) and calcium/calmodulin-dependent protein kinase (CaMKK) protein level were measured in SHR, WKY, and aortic smooth muscle (A10) cells.
  
  
  RESULTS
  α-LA (1-500 µmol/l) produced a concentration-dependent relaxation of precontracted aortic rings from 8- and 16-week-old SHR, but not in those from WKY rats. This vasodilatory effect of α-LA did not change after preincubation with N(G)-nitro-L-arginine methyl ester (100 µmol/l), but significantly suppressed by an AMPK inhibitor, compound C (40 µmol/l). The expression of pAMPKα, pLKB1, and CaMKK were also significantly reduced in endothelium-denuded arteries from 16-week-old SHR compared with those from younger SHR or age-matched WKY rats. After incubation with α-LA (100 µmol/l), the expression of pAMPKα and pLKB1 was significantly increased in the endothelium-denuded aortas from 16-week-old SHR, the expression of CaMKK was more reduced in the endothelium-denuded aortas of 8-week-old SHR, but this was not observed in WKY rats. α-LA also activated AMPKα phosphorylation in A10 cells.
  
  
  CONCLUSIONS
  The effects of α-LA on vascular relaxation in SHR result from the enhanced phosphorylation of LKB1-AMPK in aortic smooth muscle.
authors: School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan.
authors: Pao-Yun
authors: PY
authors: Cheng
authors: Yen-Mei
authors: YM
authors: Lee
authors: Ming-Tzeung
authors: MT
authors: Chung
authors: Yen-Cheng
authors: YC
authors: Shih
authors: Mao-Hsiung
authors: MH
authors: Yen
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009924:Organ Culture Techniques; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D008063:Thioctic Acid / Q000494:pharmacology*; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology; D014803:Vitamin B Complex / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D014665:Vasodilator Agents; C516138:dorsomorphin; D014803:Vitamin B Complex; D008063:Thioctic Acid; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; D019331:NG-Nitroarginine Methyl Ester