The renin angiotensin system has been shown to be involved in the patho genesis of vascular and renal sequelae of diabetes mellitus. In type 2 diabetes mel litus, angiotensin receptor blockers have been shown to exert clinical benefit by reducing the progression of diabetic nephropathy. They also improve endothelium- mediated vascular function. The latter effect is partly due to the reduction of angiotensin II-associated oxidative stress. Moreover, small clinical studies have shown that treatment with angiotensin receptor blockers also reduces the circulating levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase.
In the VIVALDI trial, the ability of the angiotensin receptor blocker telmisartan to reduce the progression of diabetic nephropathy (associated with proteinuria) in com parison with valsartan in more than 800 patients with type 2 diabetes during 1 year of treatment is being studied. In order to gain more detailed insight into the poten tial pathomechanisms associated with this effect, further end-points have been defined. Among these are the circulating levels of ADMA and the urinary excretion rate of 8-iso-prostaglandin F2α (8-iso-PGF 2α). The former is an endogenous inhibitor of NO-mediated vascular function(s) and a prospectively determined marker of major cardiovascular events and mortality; the latter is a lipid peroxidation product resulting from the nonenzymatic peroxidation of arachidonic acid, which exerts detrimental vascular effects similar to those of thromboxane A2. Urinary 8-iso-PGF 2α has been shown in clinical studies to be an independent marker of cardiovascular disease.
Highlighting the effects of telmisartan on ADMA and 8-iso-PGF levels in such a large cohort of diabetic patients will enhance our understanding of the roles of dys functional NO metabolism and redox mechanisms in the pathogenesis of end-organ damage and its prevention by pharmacotherapy with angiotensin receptor blockers.
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