NO and prostaglandin interactions during hemodynamic stress in the fetal ovine pulmonary circulation

Nitric oxide (NO) and prostacyclin (PGI(2)) are potent fetal pulmonary vaso dilators, but their relative roles and interactions in the regulation of th e perinatal pulmonary circulation are poorly understood. We compared the se parate and combined effects of nitric oxide synthase (NOS) and cyclooxygena se (COX) inhibition during acute hemodynamic stress caused by brief mechani cal compression of the ductus arteriosus (DA) in chronically prepared fetal lambs. Nitro-L-arginine (L-NNA; NOS antagonist), meclofenamate (Mec; COX i nhibitor), combined drugs (L-NNA-Mec), or saline (control) was infused into the left pulmonary artery (LPA) before DA compression. In controls, DA com pression decreased pulmonary vascular resistance (PVR) by 43% (P < 0.01). L -NNA, but not Mec, treatment completely blocked vasodilation and caused a p aradoxical increase in PVR (+31%; P < 0.05). The effects of L-NNA-Mec and L -NNA on PVR were similar. To determine if the vasodilator effect of PGI(2) is partly mediated by NO release, we studied PGI(2)-induced vasodilation be fore and after NOS inhibition. L-NNA treatment blocked the PGI(2)-induced r ise in LPA blood flow by 73% (P < 0.001). We conclude that NO has a greater role than PGs in fetal pulmonary vasoregulation during acute hemodynamic s tress and that PGI(2)-induced pulmonary vasodilation is largely mediated by NO release in the fetal lung.