Can PPAR-γ agonists have a role in the management of obesity-related hypertension?

Peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. PPAR gamma is the most extensively studied amongst the three subtypes (alpha, delta and gamma). This receptor is a key modulator of lipid and glucose horneostasis and is predominantly expressed in adipose tissue. Expression of PPAR gamma is also found in non-adipose tissues including heart, kidney, spleen, and interestingly, in all relevant components of the vasculature: endothelial and smooth muscle cells. These receptors may therefore also play a role in the regulation of vascular tone and blood pressure. Genetic variants of PPAR gamma have also been associated with features of the metabolic syndrome, including obesity and increased blood pressure. The discovery of synthetic ligands for PPAR gamma, the Thiazolidinediones (TZDs) has greatly enhanced our understanding of their ligand dependent activation and more importantly their role in vascular pathobiology. Approximately 10 years ago, serendipitous animal experiments demonstrated that despite causing sodium retention, the TZDs actually lowered blood pressure. This review will highlight the role of TZDs in various models of hypertension and discuss their potential role in the management of obesity-related hypertension. (c) 2006 Published by Elsevier Inc.