Dhvanit I Shah1, Manjeet Singh. 1. Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala-147002 Punjab India. dhvanitshah@gmail.com
Abstract
BACKGROUND: Activation of Akt stimulates phosphorylation of eNOS, production of nitric oxide and reduces oxidative stress. The study has been designed to investigate the effect of DAQ B1, an activator of Akt, in hypertension associated vascular endothelial dysfunction. METHODS: Rats were uninephroctomized and DOCA (40 mg kg(-1), s.c.) was administered to rats to produce hypertension (MABP>140 mm Hg). 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 TBARS and aortic superoxide anion were estimated to assess oxidative stress. RESULTS: DAQ B1 (5 mg kg(-1), p.o.) or atorvastatin (30 mg kg(-1), p.o.) markedly improved acetylcholine induced endothelium dependent relaxation, vascular endothelial lining, expression of mRNA for eNOS and p22phox, serum nitrite/nitrate concentration and serum TBARS in hypertensive rats. However, this ameliorative effect of DAQ B1 has been prevented by L-NAME (25 mg kg(-1), i.p.), an inhibitor of eNOS. CONCLUSION: Therefore, it may be concluded that DAQ B1 induced activation of Akt may activate eNOS and consequently reduce oxidative stress to improve hypertension associated vascular endothelial dysfunction.
BACKGROUND: Activation of Akt stimulates phosphorylation of eNOS, production of nitric oxide and reduces oxidative stress. The study has been designed to investigate the effect of DAQ B1, an activator of Akt, in hypertension associated vascular endothelial dysfunction. METHODS:Rats were uninephroctomized and DOCA (40 mg kg(-1), s.c.) was administered to rats to produce hypertension (MABP>140 mm Hg). 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 TBARS and aortic superoxide anion were estimated to assess oxidative stress. RESULTS:DAQ B1 (5 mg kg(-1), p.o.) or atorvastatin (30 mg kg(-1), p.o.) markedly improved acetylcholine induced endothelium dependent relaxation, vascular endothelial lining, expression of mRNA for eNOS and p22phox, serum nitrite/nitrate concentration and serum TBARS in hypertensiverats. However, this ameliorative effect of DAQ B1 has been prevented by L-NAME (25 mg kg(-1), i.p.), an inhibitor of eNOS. CONCLUSION: Therefore, it may be concluded that DAQ B1 induced activation of Akt may activate eNOS and consequently reduce oxidative stress to improve hypertension associated vascular endothelial dysfunction.