Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
Nitric oxide (NO) produced by NO synthase (NOS) contributes to pulmonary vasolidation and the fall in pulmonary vascular resistance (PVR) at birth. Past studies have shown that inhibition of NOS with L-arginine analogues increases basal PVR and attenuates the fall in PVR during transition, but these arginine analogues were not isoform selective. Recent studies have shown that type II or inducible NOS (NOS II) contributes to basal PVR and is predominantly expressed in fetal airway epithelium. Whether other NOS isoforms, specifically NOS II, contributes to the fall in PVR at birth is unknown. To determine if NOS II contributes to the NO-mediated fall in PVR to birth related-stimuli, we studied the pulmonary vascular effects of a selective NOS II antagonist (aminoguanidine; AG, 120mg) and a non-selective NOS antagonist (nitro-L-arginine; LNA, 20mg) during mechanical ventilation with low FiO2 (< 10%) for 60 min and to high FiO2 (100%) for 30 min in 13 fetal lambs (mean age 139 ± 2 d; term, 147 d). A catheter was placed in the left pulmonary artery (LPA) for selective drug infusion, an ultrasonic flow transducer was placed on the LPA to measure blood flow in the left lung (Q), and catheters were placed in the left atrium, main pulmonary artery, and aorta to measure pressure. Studies were performed after at least 60 min of recovery from surgery. Brief intrapulmonary infusion of AG (n=5), and LNA (n=4) increased basal PVR (p<0.05) prior to ventilation with low FiO2. In control animals (n=4), Q steadily increased during ventilation with low FiO2 and high FiO2 (see table). We conclude that AG, a selective NOS II antagonist, is as effective as non-selective NOS blockade in attenuating the rise in pulmonary artery blood flow and fall in PVR at birth. We speculate that NOS II activity may contribute to NO-mediated pulmonary vasodilation at birth.
Rairigh, R., Grover, T., Kinsella, J. et al. Aminoguanidine, a Selective Type II (Inducible) Nitric Oxide Synthase Antagonist, Attenuates Vasodilation to Birth-Related Stimuli in the Ovine Lung.
Pediatr Res45, 69 (1999). https://doi.org/10.1203/00006450-199904020-00414
