Early pravastatin treatment prevented cardiovascular remodeling in the spontaneous DM model by retarding the progression of glucose intolerance, overexpressing cardiac eNOS, and inhibiting overexpressions of fibrogenic/proinflammatory cytokines.

Ultrasonic destruction of microbubbles delivered to the ischemic limbs can recruit inflammatory cells producing VEGF, which is followed by neovascularization and functional improvement, and thus has a therapeutic potential.

iabetes mellitus (DM) and metabolic syndrome frequently result in congestive heart failure (CHF) with either preserved or unpreserved left ventricular (LV) systolic function, independent of coronary atherosclerosis. 1,2 This is because insulin resistance (IR) and impaired glucose metabolism facilitate not only coronary atherosclerosis leading to coronary events, but also myocardial interstitial fibrosis 3 and coronary microangiopathy, 4,5 at least partly through nitric oxide (NO)/superoxide imbalance. 2,4 In this regard, new-onset DM during medical treatment of hypertensive patients was reported to significantly increase the risk of cardiovascular events, including CHF, during a long-term follow-up period. 6 Therefore, attention should be paid to the influence of cardiovascular agents on glycemic control during prevention of cardiovascular diseases.The hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) have been widely prescribed to reduce cardiovascular events, based on the results of several clinical trials in which lower lipid levels were related to lower coronary event rates. 7-9 Intensive lipid-lowering therapy with atorvastatin (AS) can stop 10 or reverse 11 the further progression of coronary plaques and shows greater prevention of recurrent coronary events after acute coronary syndrome, compared with standard lipid lowering by pravastatin (PS). 9 Thus, the benefit of intensive lipid lowering to prevent coronary events by stabilizing coronary plaques has been established. However, the effects of statin therapy on glycemic control [12][13][14][15][16][17][18][19][20] or on the development of CHF have not been fully investigated and remain controversial. We have recently shown that early and long-term treatment with PS eliciting moderate lipid-lowering effects can retard the development of DM and progression of LV diastolic dysfunction, 15 a manifestation of diabetic cardiomyopathy, in a model of spontaneously developing type II DM, the Otsuka Long-Evans Tokushima Fatty (OLETF) rats. 21 However, whether intensive lipid lowering by other statins can exert greater or similar effects remains unknown. Moreover, although adipocytokines [22][23][24] have been emerging as factors affecting IR and should play an important role in the development of DM, the effects of statin therapy on them also remain to be studied.Therefore, in this study, we compared intensive lipid Background Controversy exists regarding the effects of statin therapy on progressive insulin resistance (IR) and its consequences, in the present study a rat model of spontaneously developing type II diabetes mellitus (DM) was used to examine the impact of atorvastatin (AS) vs pravastatin (PS). Methods and ResultsThe Otsuka Long-Evans Tokushima Fatty rats were either untreated or treated with 100 mg/kg per day of AS or PS from 6 weeks of age for 24 weeks. AS achieved much greater lipid lowering than PS. Serial oral glucose tolerance tests revealed new-onset diabetes was delayed by PS only. The untreated rats exhibited a progressive decrea...

No abstract

Azelnidipine is a novel dihydropyridine-type calcium antagonist with long-acting anti-hypertensive action and a low reported incidence of tachycardia. We aimed to evaluate its antioxidant activity in cultured human arterial endothelial cells under oxidative stress. Endothelial cells were exposed to 1 mM H2O2 and treated with 100 microM alpha-tocopherol, 1 nM, 10 nM or 100 nM azelnidipine, 100 nM nifedipine or 100 nM amlodipine. After 3 h, the cell number and level of lipid peroxidation were evaluated by measuring the total protein and 8-iso-PGF2 alpha concentrations, respectively. The total protein concentration was similar with each treatment. Inhibition of 8-iso-PGF2 alpha was greatest with 10 nM azelnidipine (compared with the other drugs); the difference between 10 nM and 100 nM azelnidipine was not significant. We conclude that azelnidipine has a potent antioxidative effect that could be of significant clinical benefit when combined with its long-lasting anti-hypertensive action and low incidence of tachycardia.