thromboxane-a2 and indoxam

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

Topics: Animals; Carbamates; Cells, Cultured; Cyclooxygenase 2 Inhibitors; Endothelium, Vascular; Enzyme Inhibitors; Indolizines; Isometric Contraction; Nitrobenzenes; Phospholipases A2, Secretory; Prostaglandin H2; Pulmonary Artery; Rabbits; Sulfonamides; Thromboxane A2