Quercetin Exerts Age-Dependent Beneficial Effects on Blood Pressure and Vascular Function, But Is Inefficient in Preventing Myocardial Ischemia-Reperfusion Injury in Zucker Diabetic Fatty Rats

槲皮素对血压和血管功能具有年龄依赖性的有益作用,但在预防 Zucker 糖尿病肥胖大鼠的心肌缺血-再灌注损伤方面却无效

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作者:Kristina Ferenczyova, Barbora Kalocayova, Lucia Kindernay, Marek Jelemensky, Peter Balis, Andrea Berenyiova, Anna Zemancikova, Veronika Farkasova, Matus Sykora, Lubomira Tothova, Tomas Jasenovec, Jana Radosinska, Jozef Torok, Sona Cacanyiova, Miroslav Barancik, Monika Bartekova

Background

Quercetin (QCT) was shown to exert beneficial cardiovascular effects in young healthy animals. The

Conclusions

QCT might be beneficial for vascular function in diabetes type 2; however, increasing age and/or progression of diabetes may confound its vasculoprotective effects. QCT seems to be inefficient in preventing myocardial I/R injury in type 2 diabetes and/or higher age. Impaired activation of PI3K/Akt kinase pathway might be, at least in part, responsible for failing cardioprotection in these subjects.

Methods

Lean (fa/+) and obese (fa/fa) ZDF rats of both ages were treated with QCT for 6 weeks (20 mg/kg/day). Isolated hearts were exposed to ischemia-reperfusion (I/R) injury (30 min/2 h). Endothelium-dependent vascular relaxation was measured in isolated aortas. Expression of selected proteins in heart tissue was detected by Western blotting.

Results

QCT reduced systolic blood pressure in both lean and obese 6-month-old rats but had no effect in 1-year-old rats. Diabetes worsened vascular relaxation in both ages. QCT improved vascular relaxation in 6-month-old but worsened in 1-year-old obese rats and had no impact in lean controls of both ages. QCT did not exert cardioprotective effects against I/R injury and even worsened post-ischemic recovery in 1-year-old hearts. QCT up-regulated expression of eNOS in younger and PKCε expression in older rats but did not activate whole PI3K/Akt pathway. Conclusions: QCT might be beneficial for vascular function in diabetes type 2; however, increasing age and/or progression of diabetes may confound its vasculoprotective effects. QCT seems to be inefficient in preventing myocardial I/R injury in type 2 diabetes and/or higher age. Impaired activation of PI3K/Akt kinase pathway might be, at least in part, responsible for failing cardioprotection in these subjects.

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