Inhibition of untransformed prostaglandin H2 production and stretch-induced contraction of rabbit pulmonary arteries by indoxam,a selective secretory phospholipase A2 inhibitor

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. © the japanese pharmacological society.