ABSTRACT
Objective: To investigate the effect of combined hypoxia and high fat diet (HFD) on endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) of myocardium in experimental rats with its possible mechanisms. Methods: A total of 60 male SD rats were randomly divided into 3 groups, n=20 in each group. Control group, the rats were fed by normal diet with normal oxygen condition. Hypoxia group, the rats were fed by normal diet with simulated 5000m altitude oxygen condition. Combined hypoxia and HFD (H+HFD) group, the rats were fed by HFD and simulated 5000m altitude oxygen condition. All animals were treated for 4 weeks and peripheral blood and myocardium specimen were collected. Hemoglobin was examined by automatic blood cell analyzer, plasma malondialdehyde (MDA) was measured by TBA method, superoxide dismutase (SOD) activity was detected by WST-1 method, mRNA and protein expressions of eNOS were examined by real time PCR and Western blot analysis respectively, the myocardium nitrates and nitrites (NOx) was measured by nitrate reductase method. Results: Compared with Control group, Hypoxia group and H+HFD group had increased mRNA and protein expressions of eNOS, H+HFD group had lower NOx levels than the other 2 groups P Conclusion: Upon hypoxia alone, H+HFD may further reduce NOx level of myocardium, it implies aggravated chronic hypoxia impairment, which might be related to dyslipidemia and lack of anti-oxidative ability in experimental rats.
ABSTRACT
This study is to investigate the effect of high altitude hypoxia on the activity and protein expression of CYP2C9 and CYP2C19. Rats from plain (P) and rats with acute middle altitude hypoxia (AMH), chronic middle altitude hypoxia (CMH), acute high altitude hypoxia (AHH) and chronic high altitude hypoxia (CHH) were administered orally phenytoin sodium (PHT) and omeprazole (OMZ) to evaluate the activity of CYP2C9 and CYP2C19, separately. The serum concentrations of PHT and metabolite 4'-hydroxyphenytoin (HPPH) at 12 h after treatment and the serum concentrations of OMZ and metabolite 5-hydroxy omeprazole (5-OHOMZ) at 3 h after treatment were determined by RP-HPLC. The activity of CYP2C9 and CYP2C19 was evaluated by the ratio of HPPH to PHT and the ratio of 5-OHOMZ to OMZ, respectively. The protein expressions of CYP2C9 and CYP2C19 were determined by ELISA method. The activities of CYP2C9 (HPPH/PHT) in P, AMH, CMH, AHH and CHH were 0.67 +/- 0.31, 0.75 +/- 0.29, 0.76 +/- 0.23, 0.79 +/- 0.31 and 0.75 +/- 0.18, respectively, and the activities of CYP2C19 (5-OHOMZ/OMZ) in P, AMH, CMH, AHH and CHH were 0.17 +/- 0.06, 0.20 +/- 0.10, 0.11 +/- 0.05, 0.37 +/- 0.13 and 0.19 +/- 0.05, respectively. The protein expressions of CYP2C9 in P, AMH, CMH, AHH and CHH were 4.20 +/- 1.27, 3.95 +/- 0.81, 3.93 +/- 1.11, 4.32 +/- 1.03 and 4.12 +/- 0.86 ng x g(-1), respectively, and the protein expressions of CYP2C19 in P, AMH, CMH, AHH and CHH were 3.91 +/- 1.82, 3.63 +/- 2.07, 2.55 +/- 0.85, 4.78 +/- 2.37 and 3.51 +/- 1.03 ng x g(-1), respectively. The activities and protein expressions of CYP2C9 in AMH, CMH, AHH and CHH were not significantly different with those of P. The protein expressions of CYP2C19 in AMH, CMH, AHH and CHH were not significantly different with those of P, but the activity of CYP2C19 in AHH was significantly higher than that of P. This study found significant changes in the activity of CYP2C19 under the special environment of acute high altitude hypoxia.