ROLE OF ENDOGENOUS NITRIC OXIDE SYNTHASE INHIBITION IN PERSISTENT PULMONARY HYPERTENSION OF THE NEWBORN (PPHN). 464

Abstract

Nitric oxide is believed to be responsible for the normal 8 to 10 fold decrease in the pulmonary vascular resistance that occurs during the transition at birth from fetal to postnatal circulation. NO is produced in the endothelial cells from L-arginine by nitric oxide synthase (NOS). Chronic inhibition of NOS in utero by L-arginine analogs results in PPHN(Fineman, JCI, 1994). The existence of endogenous arginine analogs such as N-monomethyl L-arginine (L-NMMA) has been demonstrated by Vallance et al.(1991) who suggested that its accumulation in chronic renal failure may be responsible for systemic hypertension. To determine the role by endogenous L-NMMA inhibition of NOS in PPHN, we collected aortic blood samples at 0, 15, 60, 240 and 420 minutes after birth from control lambs and lambs in whom PPHN was induced by prenatal ductal ligation. The assay for L-NMMA was carried out by high performance liquid chromatography (HPLC) after derivatization with dabsyl chloride. ˙V NO was measured from expired gas by chemiluminescence.Figure