Vascular protection in diabetes: a pharmacological view of angiotensin II type 1 receptor blockers

Vascular protection is key to reducing the morbidity associated with diabetes. Angiotensin II is known to exert a variety of deleterious effects on the vasculature, and this is likely to be a major explanation of the protective benefits observed with blockade of the renin-angiotensin-aldosterone system (RAAS). Intriguingly, RAAS blockade also appears to reduce the onset of new diabetes, which points to a fundamental effect on metabolism. Recent developments have thrown new light onto the mechanism of these effects. The importance of unopposed stimulation of the angiotensin II type 2 (AT(2)) receptor in vascular protection is recognised, and recent studies have revealed that some angiotensin II type 1 (AT(1)) receptor blockers (ARBs) show partial peroxisome proliferator-activated receptor-gamma (PPARgamma) agonistic activity in vitro, an effect that is at least partly due to direct interaction with PPARgamma itself. There is a clear order of potency among the ARBs, with telmisartan the most potent and the only ARB to show an effect at physiologically achievable plasma concentrations. Adiponectin, an adipokine closely involved with glucose sensitisation, is also modulated by the relative activation of AT(1) and AT(2) receptors. Such effects would suggest that important benefits may result from the use of ARBs in clinical practice, although confirmation of the clinical relevance will depend upon the results of numerous ongoing studies.