Possible role of Akt to improve vascular endothelial dysfunction in diabetic and hyperhomocysteinemic rats

Mol Cell Biochem. 2007 Jan;295(1-2):65-74. doi: 10.1007/s11010-006-9273-9. Epub 2006 Jul 14.

Abstract

The study has been designed to investigate the effect of demethylasterroquinone B1 (DAQ B1), an activator of Akt, in diabetes mellitus (DM) and hyperhomocysteinemia (HHcy)-induced vascular endothelial dysfunction. Streptozotocin (55 mg kg(-1), i.v.) and methionine (1.7% w/w, p.o., 4 weeks) were administered to rats to produce DM (serum glucose >140 mg dl(-1)) and HHcy (serum homocysteine >10 microM), respectively. Vascular endothelial dysfunction was assessed using isolated aortic ring preparation, electron microscopy of thoracic aorta and serum concentration of nitrite/nitrate. The expression of messenger RNA for p22phox and eNOS was assessed by reverse transcription-polymerase chain reaction. Serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion were estimated to assess oxidative stress. DAQ B1 (5 mg kg(-1), p.o.) or atorvastatin (30 mg kg(-1), p.o.) in diabetic and hyperhomocysteinemic rats significantly reduced serum glucose and homocysteine concentration. DAQ B1 or atorvastatin markedly improved acetylcholine-induced endothelium-dependent relaxation, vascular endothelial lining, serum nitrite/nitrate concentration and serum TBARS in diabetic and hyperhomocysteinemic rats. However, this ameliorative effect of DAQ B1 has been prevented by L-NAME (25 mg kg(-1), i.p.), an inhibitor of eNOS. Therefore, it may be concluded that DAQ B1-induced activation of Akt may activate eNOS and consequently reduce oxidative stress to improve vascular endothelial dysfunction.

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Aorta / drug effects
  • Aorta / enzymology
  • Aorta / ultrastructure
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / enzymology*
  • Diabetes Mellitus, Experimental / physiopathology*
  • Endothelium, Vascular / enzymology*
  • Endothelium, Vascular / physiopathology*
  • Endothelium, Vascular / ultrastructure
  • Gene Expression Regulation, Enzymologic / drug effects
  • Homocysteine / blood
  • Hyperhomocysteinemia / chemically induced
  • Hyperhomocysteinemia / enzymology*
  • Hyperhomocysteinemia / physiopathology*
  • Male
  • NADPH Oxidases / genetics
  • NADPH Oxidases / metabolism
  • Nitrates / blood
  • Nitric Oxide Synthase Type III / genetics
  • Nitric Oxide Synthase Type III / metabolism
  • Nitrites / blood
  • Proto-Oncogene Proteins c-akt / agonists
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Quinones / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Superoxides / metabolism
  • Thiobarbituric Acid Reactive Substances / analysis
  • Vasodilation / drug effects

Substances

  • Blood Glucose
  • Nitrates
  • Nitrites
  • Quinones
  • RNA, Messenger
  • Thiobarbituric Acid Reactive Substances
  • Homocysteine
  • Superoxides
  • Nitric Oxide Synthase Type III
  • NADPH Oxidases
  • Cyba protein, rat
  • Proto-Oncogene Proteins c-akt
  • Acetylcholine