Amlodipine Inhibits Vascular Cell Senescence and Protects Against Atherogenesis Through the Mechanism Independent of Calcium Channel Blockade.

Vascular cells have a finite lifespan and eventually enter irreversible growth arrest called cellular senescence. We have previously suggested that vascular cell senescence contributes to the pathogenesis of human atherosclerosis. Amlodipine is a mixture of two enantiomers, one of which (S- enantiomer) has L-type channel blocking activity, while the other (R+ enantiomer) shows ~1000-fold weaker channel blocking activity than S- enantiomer and has other unknown effects. It has been reported that amlodipine inhibits the progression of atherosclerosis in humans, but the molecular mechanism of this beneficial effect remains unknown. Apolipoprotein E-deficient mice on a high-fat diet were treated with amlodipine, its R+ enantiomer or vehicle for eight weeks. Compared with vehicle treatment, both amlodipine and the R+ enantiomer significantly reduced the number of senescent vascular cells and inhibited plaque formation to a similar extent. Expression of the pro-inflammatory molecule interleukin-1ß was markedly upregulated in vehicle-treated mice, but was inhibited to a similar extent by treatment with amlodipine or the R+ enantiomer. Likewise, activation of p53 (a critical inducer of senescence) was markedly suppressed by treatment with amlodipine or the R+ enantiomer. These results suggest that amlodipine inhibits vascular cell senescence and protects against atherogenesis at least partly by a mechanism that is independent of calcium channel blockade.

Smoking was a Possible Negative Predictor of Incident Hypertension After a Five-Year Follow-up Among a General Japanese Population.

BACKGROUNDS: The association between cigarette smoking and hypertension is controversial. The aim of this study is to investigate the association between smoking and incident hypertension. METHODS: This is a post-hoc five-year follow-up study in a general Japanese population. Logistic regressions were performed using incident hypertension as an outcome and smoking status as an independent predictor adjusting for sex, age, body mass index (BMI), total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, fasting plasma glucose (FPG), drinking status, and diabetes in 1,297 subjects without hypertension at baseline. RESULTS: The incidence of hypertension was 16.9% vs. 27.6% (smokers vs. nonsmokers, P = 0.01) in men and 0.0% vs. 16.9% (smokers vs. nonsmokers, P = 0.03) in women. The odds ratio (OR) (95% confidence interval (CI)) of incident hypertension was 0.38 (0.19 - 0.76) (P = 0.006) for smokers at baseline, 0.33 (0.16 - 0.68) (P = 0.003) for continuing smokers, and 2.11 (0.33 - 13.45) (P = 0.4) for ex-smokers. Age (OR = 1.52, P < 0.0001), BMI (OR = 1.46, P < 0.0001), and FPG (OR = 1.23, P = 0.007) were other independent predictors of incident hypertension. CONCLUSIONS: Smoking was a possible significant negative predictor of incident hypertension in a general Japanese population.