Ovine bronchial-derived relaxing factor: changes with development and hyperoxic ventilation

Recent studies suggest that a bronchial-derived relaxing factor (BrDRF) decreases the contractility of newborn, but not fetal, rat pulmonary arteries (PAs) by a nitric oxide (NO)-mediated mechanism. We studied the effect of an adjacent bronchus on PA contractility to norepinephrine (NE) in late-gestation fetal ( n = 7), neonatal (1 day old, n = 9), ventilated neonatal (24-h ventilation from birth with 100% oxygen, n = 9), and adult sheep ( n = 6) in the presence and absence of the NO synthase inhibitor Nω-nitro-l-arginine (l-NNA). The sheep were anesthetized and killed, and fifth-generation PA rings with and without an attached adjacent bronchus (PA+Br) were contracted in standard tissue baths with NE (10−8–10−6 M). NE contractions were expressed as fraction of KCl (118 mM) contraction and as grams of contraction force. NE contractions were significantly diminished by the presence of an attached bronchus in the neonatal and ventilated neonatal and adult, but not fetal, lambs. Hyperoxic ventilation markedly increased NE contractions in PA and PA+Br. l-NNA significantly enhanced NE contractions in PA+Br in postnatal but not in fetal lambs. Pretreatment with l-NNA abolished the difference between NE contractions in PA and PA+Br in neonatal but not in hyperoxic ventilated neonatal lambs. We conclude that there is a BrDRF that is developmentally regulated and has vascular activity postnatally but not during fetal life. The effect of BrDRF is predominantly mediated by NO in air-breathing neonatal lambs but may involve a second non-NO mediator following hyperoxic ventilation. We speculate that BrDRF may have an important role in postnatal changes in pulmonary arterial reactivity.