Journal of cardiovascular pharmacology
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Diabetes mellitus is associated with accelerated atherosclerosis and an increased prevalence of cardiovascular disease. Although the link between diabetes and cardiovascular disease is not fully understood, loss of the modulatory role of the endothelium could be implicated in the pathogenesis of diabetic vascular complications. There is substantial evidence that vasodilatation mediated by endothelium-derived nitric oxide (NO) is impaired in animal models of diabetes and in patients with insulin-dependent and non-insulin-dependent diabetes mellitus. ⋯ Hyperglycemia-induced endothelial dysfunction may result from decreased production of NO, inactivation of NO by oxygen-derived free radicals, and/or increased production of endothelium-derived contracting factors, which oppose the protective activity of NO. This review summarizes evidence for endothelial dysfunction in diabetic patients and animals and the effects of prolonged exposure to elevated glucose in normal blood vessels and cultured endothelium. A better understanding of the mechanism(s) of hyperglycemia-induced endothelial dysfunction may unmask new preventive strategies to reduce cardiovascular morbidity and mortality in this condition.
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J. Cardiovasc. Pharmacol. · Jan 1998
Myocardial protection afforded by nicorandil and ischaemic preconditioning in a rabbit infarct model in vivo.
We previously showed that preoperative nicorandil, a hybrid potassium channel opener and nitrate compound, conferred cardioprotective effects in a hypoxia/reoxygenation model of isolated human atrial muscle by using functional recovery as an end point, and that ischaemic preconditioning surprisingly abolished the protection afforded by nicorandil. In view of this paradoxic result, this study was undertaken to assess whether ischaemic preconditioning influences any protective effect of nicorandil by using infarct size as an end point. In addition, we investigated the underlying mechanisms of the protective action of nicorandil. ⋯ Our results show that nicorandil has a protective effect against myocardial infarction in our rabbit model when infused before and during ischaemia, but not during reperfusion, and the protective effect is abolished by an ATP-sensitive potassium channel blocker. Furthermore, the addition of ischaemic preconditioning does not detrimentally influence the effect of nicorandil. This suggests that nicorandil can confer an infarct-limiting effect by opening of ATP-sensitive potassium channels with or without intermittent ischaemia, as may happen in patients with unstable angina.