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

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.

• Authors: Dhvanit I Shah, Manjeet Singh
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 295 Issue 1-2 Pg. 65-74 (Jan 2007) ISSN: 0300-8177 [Print] Netherlands
• PMID: 16841179 (Publication Type: Journal Article)

Chemical References

• 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

Topics

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