Abstract
A low concentration of nitric oxide associated with a high concentration of asymmetric dimethylarginine (ADMA) can explain the lack of ischemic cardioprotection observed in the presence of hypercholesterolemia. The objective of the present study was to evaluate the effect of hypercholesterolemia on ischemic pre- and postconditioning and its correlation with plasma concentrations of ADMA. Male Wistar rats (6-8 weeks old) fed a 2% cholesterol diet (n = 21) for 8 weeks were compared to controls (n = 25) and were subjected to experimental myocardial infarction and reperfusion, with ischemic pre- and postconditioning. Total cholesterol and ADMA were measured in plasma before the experimental infarct and the infarct area was quantified. Weight, total cholesterol and plasma ADMA (means ± SE; 1.20 ± 0.06, 1.27 ± 0.08 and 1.20 ± 0.08 vs 0.97 ± 0.04, 0.93 ± 0.05 and 0.97 ± 0.04 µM) were higher in animals on the hypercholesterolemic diet than in controls, respectively. Cardioprotection did not reduce infarct size in the hypercholesterolemic animals (pre: 13.55% and post: 8% compared to 7.95% observed in the group subjected only to ischemia and reperfusion), whereas infarct size was reduced in the animals on a normocholesterolemic diet (pre: 8.25% and post: 6.10% compared to 12.31%). Hypercholesterolemia elevated ADMA and eliminated the cardioprotective effects of ischemic pre- and postconditioning in rats.
Highlights
The literature is not unanimous about the influence of hypercholesterolemia on the infarct size after ischemic pre- and postconditioning
A low concentration of nitric oxide associated with a high concentration of asymmetric dimethylarginine (ADMA) can explain the lack of ischemic cardioprotection observed in the presence of hypercholesterolemia
Cardioprotection did not reduce infarct size in the hypercholesterolemic animals, whereas infarct size was reduced in the animals on a normocholesterolemic diet
Summary
The literature is not unanimous about the influence of hypercholesterolemia on the infarct size after ischemic pre- and postconditioning. The limiting effect of infarct size caused by this form of cardioprotective ischemia is attenuated in rabbits fed a diet enriched with up to 1% cholesterol [2]. There are reports based on research with animals that did not demonstrate an influence of hyperlipidemia on the beneficial effects of classical ischemic preconditioning [3,4,5,6]. Some studies have shown the lack of beneficial effects of postconditioning in animals with experimental hyperlipidemia [3]. Donato et al [7] showed a reduction of myocardial damage in a model of experimental myocardial infarction and hypercholesterolemia involving rabbits subjected to ischemic postconditioning
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