Several animal models have shown NO donors to counter the effects of maternal nutrient restriction and prevent the development of hypertension in offspring. There are several classes of drug that may improve endothelial function, as described below.
The inter-relationship between the components of the metabolic syndrome is epitomized by the actions of statins. These were employed originally to reduce the incidence of CHD because of their efficacy in lowering lipid levels. Several other actions that may be protective are now apparent (Endres and Laufs, 2004). Statins appear to improve endothelial function by promoting NO production via increased synthesis of eNOS. They also may increase NO bioavailability by reducing oxidative stress. Other actions include the observation of lower levels of inflammatory mediators such as TNF-a and IL-6 and the ability to improve arterial compliance (Endres and Laufs, 2004; Matsuo etal., 2005). These actions may be responsible for up to a 30 per cent reduction in the risk of developing type 2 diabetes (Rosenson, 1999). Angiotensin-converting enzyme (ACE) inhibitors have also been demonstrated to increase NO bioavailability (Henriksen and Jacob, 2003), and a decrease in the progression of impaired glucose tolerance to type 2 diabetes was an unexpected finding when they were used to treat CVD in the HOPE study (HOPE Study Investigators, 2000).
Thiazolidinediones (TZDs) reduce insulin resistance in the peripheral tissues. This allows the effects of decreasing insulin resistance on vascular function to be studied. Activation of PPARy within endothelial cells may explain why TZDs appear to bolster antioxidant activity. This reduction in oxidative stress is thought to be responsible for a decrease in inflammation, improvement of endothelial function and VSMC proliferation (Gonzalez and Selwyn, 2003). In vitro and in vivo studies have shown the potential of TZDs to prevent or delay atherosclerosis, and improvements have been noted in markers of endothelial function in parallel with improved insulin action (Caballero, 2003). Long-term trials with TZDs to measure cardiovascular end-points are in progress.
In theory, antioxidants should increase NO bioavailability, improve endothelial protection and function, reduce lipid peroxidation and reduce telomere shortening. Although observational studies of nutritional sources suggest some improvement, clinical trials using supplements have yet to demonstrate any benefit. A more promising strategy may be to prevent the activation of pro-oxidant enzymes such as NADPH oxidase. Certainly experimental work suggests that ACE inhibitors and statins achieve this and it may represent one of the modalities by which these drugs improve endothelial dysfunction (Pearson etal., 2003).
Clinical trials of folate are ongoing. Recent evidence suggests hyperhomocystei-naemia to be an important cause of endothelial dysfunction. Folate appears to reduce methionine levels in hyperhomocysteinaemia, reverse endothelial dysfunction and may reduce inflammation (Das, 2003). Like other facets of chronic disease, hyperhomocysteinaemia does not appear to be an independent risk factor but its use may have a role in the primary prevention of CVD.
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Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...