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

Autor: Laurent Storme, Thomas A. Parker, John Kinsella, Robyn L. Rairigh, Steven H. Abman, Theresa R. Grover, Jeanne Zenge
Rok vydání: 2001
Předmět:
Zdroj: American Journal of Physiology-Lung Cellular and Molecular Physiology. 281:L1157-L1163
ISSN: 1522-1504
1040-0605
DOI: 10.1152/ajplung.2001.281.5.l1157
Popis: Nitric oxide (NO) and prostacyclin (PGI2) are potent fetal pulmonary vasodilators, but their relative roles and interactions in the regulation of the perinatal pulmonary circulation are poorly understood. We compared the separate and combined effects of nitric oxide synthase (NOS) and cyclooxygenase (COX) inhibition during acute hemodynamic stress caused by brief mechanical compression of the ductus arteriosus (DA) in chronically prepared fetal lambs. Nitro-l-arginine (l-NNA; NOS antagonist), meclofenamate (Mec; COX inhibitor), combined drugs (l-NNA-Mec), or saline (control) was infused into the left pulmonary artery (LPA) before DA compression. In controls, DA compression decreased pulmonary vascular resistance (PVR) by 43% ( P < 0.01). l-NNA, but not Mec, treatment completely blocked vasodilation and caused a paradoxical increase in PVR (+31%; P < 0.05). The effects ofl-NNA-Mec and l-NNA on PVR were similar. To determine if the vasodilator effect of PGI2 is partly mediated by NO release, we studied PGI2-induced vasodilation before and after NOS inhibition. l-NNA treatment blocked the PGI2-induced rise 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 stress and that PGI2-induced pulmonary vasodilation is largely mediated by NO release in the fetal lung.
Databáze: OpenAIRE