PPARbeta/delta agonists GW0742 and GW501516 induce vasodilatation of human pulmonary artery

Pulmonary arterial hypertension is defined as a mean pulmonary artery pressure of greater than 25mmHg at rest. Current therapies modulate or mimic endogenous hormones released by endothelial cells that regulate vascular tone. These include prostacyclin (IP) receptor agonists (e.g. treprostinil sodium), phosphodiesterate type 5 inhibitors (e.g. sildenafil), and endothelin receptor antagonists (e.g. bosentan). However, none of these drugs cure the condition and new therapeutic approaches are currently under investigation. We and others have recently shown that the PPARbeta/delta agonist GW0742 induces vasodilatation of mouse and rat pulmonary arteries (Harrington et al 2010; Li et al 2012). However, the effect of PPARbeta/delta agonists on human pulmonary vessels has not been tested. Here we investigated the effects of two PPARbeta/delta agonists on human pulmonary artery tone in vitro using resting pressures in line with those seen in patients with pulmonary hypertension