Junko Tatebe

A comparison of the hypotensive and hypoglycaemic actions of an angiotensin converting enzyme inhibitor, an AT1a antagonist and troglitazone.

Objective To define the relationship between changes in insulin sensitivity and attenuation of hypertension. Methods We investigated whether troglitazone (CS-045, an insulin sensitizer) has an antihypertensive effect in fructose (FRU)-fed Wistar rats with insulin resistance and simultaneously compared its hypotensive efficacy with those of alacepril (ALA, an angiotensin converting enzyme inhibitor) and TCV-116 (an AT1a receptor antagonist). Male rats aged 8 weeks were divided into five groups: controls fed normal chow, a FRU group fed FRU-rich (55%) chow, a FRU plus ALA group fed 30 mg/kg ALA per day, a FRU plus TCV-116 group fed 1 mg/kg TCV-116 per day and a FRU plus CS-045 group fed 70 mg/kg CS-045 per day). After 8 weeks, the body weight and systolic blood pressure were recorded and glucose tolerance was determined by glucose loading (2g/kg, intraperitoneally) and a steady-state plasma glucose (SSPG) method. The plasma membrane glucose transporter 4 content in gastrocnemius muscle was determined by Western blot analysis. Results FRU increased blood pressure from 125 mmHg in controls to 141 mmHg (P<0.01). ALA and TCV-116 administration decreased blood pressure to 111 and 107 mmHg, respectively (P<0.01). CS-045 administration lowered blood pressure significantly to 121 mmHg. Area under the curve levels for plasma insulin during glucose loading increased from 1.7 in controls to 3.6ng/ml×h in FRU-fed rats, but were lowered by the three drugs. SSPG levels increased from 12.5 in controls to 18.3mmol/l in FRU-fed rats (P<0.01), but were decreased by ALA and TCV-116 administration (P<0.01). CS-045 administration also lowered SSPG levels to 15.3mmol/l (P<0.05). FRU-feeding induced a 1.24-fold increase in plasma membrane glucose transporter 4, which was not affected by ALA and TCV-116 administration, but was augmented 1.82-fold by CS-045 administration. Furthermore, the increased triglyceride level after FRU was diminished both by ALA and by CS-045 administration. Conclusion These results suggest that, in the insulin-resistant state, troglitazone, an angiotensin converting enzyme inhibitor and an AT1a receptor antagonist show comparable hypotensive and hypoglycaemic effects.

Molecular Hydrogen Alleviates Cellular Senescence in Endothelial Cells.

BACKGROUND Substantial evidence indicates that molecular hydrogen (H2) has beneficial vascular effects because of its antioxidant and/or anti-inflammatory effects. Thus, hydrogen-rich water may prove to be an effective anti-aging drink. This study examined the effects of H2on endothelial senescence and clarified the mechanisms involved. METHODSANDRESULTS Hydrogen-rich medium was produced by a high-purity hydrogen gas generator. Human umbilical vein endothelial cells (HUVECs) were incubated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for various time periods in normal or hydrogen-rich medium. The baseline H2concentration in hydrogen-rich medium was 0.55±0.07 mmol/L. This concentration gradually decreased, and H2was almost undetectable in medium after 12 h. At 24 h after TCDD exposure, HUVECs treated with TCDD exhibited increased 8OHdG and acetyl-p53 expression, decreased nicotinamide adenine dinucleotide (NAD(+))/NADH ratio, impaired Sirt1 activity, and enhanced senescence-associated β-galactosidase. However, HUVECs incubated in hydrogen-rich medium did not exhibit these TCDD-induced changes accompanying Nrf2 activation, which was observed even after H2was undetectable in the medium. Chrysin, an inhibitor of Nrf2, abolished the protective effects of H2on HUVECs. CONCLUSIONS H2has long-lasting antioxidant and anti-aging effects on vascular endothelial cells through the Nrf2 pathway, even after transient exposure to H2. Hydrogen-rich water may thus be a functional drink that increases longevity. (Circ J 2016; 80: 2037-2046).

Antioxidant nutrients in plasma of Japanese patients with chronic obstructive pulmonary disease (COPD), asthma-COPD overlap syndrome, and bronchial asthma.

Few studies to date have investigated the antioxidant nutrients such as vitamin C (ascorbic acid), vitamin E (α‐tocopherol), retinol and carotenoids in plasma from patients with pulmonary disease in Japan. To clarify the role of antioxidant nutrients such as vitamin C, vitamin E, retinol and various carotenoids in plasma of Japanese patients with chronic obstructive lung diseases (COPD), asthma‐COPD overlap syndrome (ACOS) and/or bronchial asthma (BA), we compared to healthy elderly controls.

Curcumin Inhibits Age-Related Vascular Changes in Aged Mice Fed a High-Fat Diet

Inhibiting the onset of arteriosclerotic disease, which has been increasing due to the westernized diet and aging, is a significant social challenge. Curcumin, a type of polyphenol, has anti-oxidative effects and anti-inflammatory action and is expected to treat and to have prophylactic effects on different diseases. In this study, we examined the effects of long-term administration of curcumin on vascular aging and chronic inflammation—the causes of arteriosclerotic disease. Eight-week-old C57BL/6J mice were fed with high fat diet (HFD) or 0.1% curcumin-mixed HFD (HFD + Cu) until 80 weeks old (n = 20 for each group). After the breeding, we examined the expression of antioxidant enzymes, heme oxygenase-1 (HO-1), oxidative stress, vascular aging, and inflammatory changes in the aorta. In the HFD group, oxidative stress increased with decreased sirt1 expression in the aorta followed by increased senescent cells and enhanced inflammation. Whereas in the HFD + Cu group, HO-1 was induced in the aorta with the suppression of oxidative stress. Additionally, it was shown that sirt1 expression in the aorta in the HFD + Cu group remained at a level comparable to that of the 8-week-old mice with suppression of increased senescent cells and enhanced inflammation. Consequently, disorders associated with HFD were resolved. These results suggest that curcumin might be a food with a prophylactic function against arteriosclerotic disease.

Prognostic Utility of Indoxyl Sulfate for Patients with Acute Coronary Syndrome

Aim: We investigated whether indoxyl sulfate (IS), a protein-bound uremic toxin, predicts prognosis after acute coronary syndrome (ACS). Methods: Serum IS level was determined prospectively in 98 patients who underwent successful primary percutaneous coronary intervention for ACS. Patients on hemodialysis were excluded. The endpoint of this study was six-month composite events including death, nonfatal myocardial infarction, heart failure requiring hospitalization, and adverse bleeding events. Results: During the mean follow-up period of 168 days, composite events occurred in 13.3% of cases. Serum IS level was significantly higher in subjects who developed composite events than in those without events (0.14 ± 0.11 mg/dl vs. 0.06 ± 0.04 mg/dl; p < 0.001). After adjusting for confounding factors, a Cox proportional hazard analysis revealed that the IS level (hazard ratio (HR): 10.6; 95% confidence interval (CI): 1.63–69.3, p = 0.01), hemoglobin level (HR: 0.61; 95% CI: 0.43–0.87; p < 0.01), and left ventricular ejection fraction (LVEF) (HR: 0.95; 95% CI: 0.91–0.99; p = 0.03) were independent predictive factors of composite events. Furthermore, IS level significantly conferred additional value to the combined established risks of LVEF and hemoglobin level for predicting the incidence of composite events (area under the curve: 0.82 vs. 0.88, p = 0.01; net reclassification improvement: 0.67, p = 0.01; and integrated discrimination improvement: 0.15, p < 0.01). Conclusions: The assessment of serum IS level has prognostic utility for the management of ACS.