See related article, pages 69–78 Peroxisome proliferator activator receptors (PPARs) are nuclear receptors that exert effects on lipid and carbohydrate metabolism. Three members of the PPAR family have been identified: α, β/δ, and γ. PPAR-α and PPAR-β/δ regulate genes that play a role in lipid metabolism and fatty acid oxidation. PPAR-γ is expressed mostly in adipose tissue, controls adipocyte differentiation and lipid storage, and sensitizes tissues to the action of insulin. PPAR-γ is also abundantly expressed in the arterial tree. Natural ligands of PPAR-γ include free fatty acids and prostaglandin D2 derivatives such as 15-deoxy-Δ12, 14-prostaglandin J2 (15d-PGJ2). Synthetic ligands for PPAR-γ include the thiazolidinediones (glitazones), which are insulin sensitizers used for treatment of diabetes mellitus. Activation of PPAR-γ with thiazolidinediones has been shown to result in abrogation of effects of angiotensin (Ang) II in rats. PPAR-γ ligands (rosiglitazone and pioglitazone) prevented development of hypertension in Ang II–infused rats, regressed vascular remodeling, reduced vascular inflammation, and improved endothelial function.1 Vascular DNA synthesis, nuclear factor (NF)-κB activity and expression of cell cycle proteins, Ang II type 1 receptors, vascular cell adhesion molecule (VCAM)-1, and platelet and endothelial cell adhesion molecule (PECAM), which were increased by Ang II infusion, were blunted by pioglitazone or rosiglitazone. This suggested that PPAR-γ could act as an endogenous Ang II antagonist, modulating the effects of the renin–angiotensin–aldosterone system. Similar effects were found in a mineralocorticoid hypertensive model, the deoxycorticosterone (DOCA)-salt rat, which is associated with activation of the endothelin system and in which the effects of PPAR-γ ligands like rosiglitazone on remodeling, oxidative stress, and inflammatory mediators could also be attributed …