ACUTE HYPOXIA INCREASES PULMONARY ARTERY INDUCIBLE NITRIC OXIDE SYNTHASE IN NEONATAL PIGLETS. † 362

Abstract

We previously demonstrated that administration of aminoguanidine, a selective inhibitor of inducible nitric oxide synthase (iNOS), in neonatal piglets increased pulmonary vascular resistance (PVR) while leaving systemic vascular resistance (SVR) unchanged during acute hypoxia, and had no effect on either PVR or SVR in normoxia. Thus, endogenous nitric oxide (NO) production in the pulmonary bed may be selectively increased via stimulated iNOS activity during hypoxia. In this study, the presence of iNOS in the pulmonary vasculature of piglets (5-7 days old) during hypoxia exposure versus normoxia was assessed. Anesthetized piglets were ventilated with room air (normoxia controls, FiO2=0.21) or exposed to acute hypoxia (FiO2=0.15) for 60 or 120 minutes. At the end of exposure, 3rd-4th generation pulmonary arterial (PA) sections were harvested and cleared of connective tissue. Western Blot analysis with a polyclonal antibody to iNOS was used to detect the presence of this specific isoform of NOS. Results showed the presence of iNOS protein in PA segments at 60 and 120 minutes of acute hypoxic exposure, with no iNOS detected in PA obtained from normoxia controls. Increased iNOS levels in the pulmonary bed and consequent increases in endogenous NO may help counteract the effects of other mediators of hypoxia-induced pulmonary vasoconstriction.