Inhibition of Untransformed Prostaglandin H2 Production and Stretch-Induced Contraction of Rabbit Pulmonary Arteries by Indoxam, a Selective Secretory Phospholipase A2 Inhibitor

Abstract

Involvement of secretory phospholipase A2 (sPLA2) in the stretch-induced production of untransformed prostaglandin H2 (PGH2) in the endothelium of rabbit pulmonary arteries was investigated. The stretch-induced contraction was significantly inhibited by indoxam, a selective inhibitor for sPLA2, and NS-398, a selective inhibitor for cyclooxygenase-2 (COX-2). Indoxam inhibited the RGD-sensitive-integrin–independent production of untransformed PGH2, but did not affect the RGD-sensitive-integrin–dependent production of thromboxane A2 (TXA2). These results suggest that the stretch-induced contraction and untransformed PGH2 production was mediated by sPLA2–COX-2 pathway, making it a new possible target for pharmacological intervention of pulmonary artery contractility. Keywords:: stretch-induced pulmonary artery contraction, secretory phospholipase A2 (sPLA2), indoxam