Role of Superoxide Anion on Basal and Stimulated Nitric Oxide Activity in Neonatal Piglet Pulmonary Vessels

Abstract

The superoxide anion (O 2 ⅐Ϫ ) appears to be an important modulator of nitric oxide bioavailability. Enzymatic scavenging of O 2 ⅐Ϫ is carried out by superoxide dismutase (SOD). The present study was designed to characterize the developmental changes on pulmonary vascular reactivity induced by 1) exogenous Cu/Zn SOD, 2) several putative SOD mimetics, and 3) endogenous SOD inhibition. We also analyzed age-related changes on pulmonary SOD activity and vascular O 2 ⅐Ϫ levels. SOD (1-300 U/mL) produced endotheliumdependent relaxation of U46619-contracted intrapulmonary arteries (fourth branch) and veins from 12-to 24-h-old and 2-wk-old piglets. SOD-induced relaxation was greater in pulmonary arteries and was abolished by the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester. SOD induced a greater pulmonary artery relaxation in the 2-wk-old than in the 12-to 24-h-old piglet. SOD (100 U/mL) did not modify acetylcholine-induced relaxation in pulmonary arteries. In contrast, endogenous SOD inhibition by diethyldithiocarbamate (3 mM) impaired acetylcholine-induced relaxation in pulmonary arteries from newborn but not from 2-wk-old piglets. Total SOD activity in lung tissue did not change with postnatal age. With the use of dihydroethidium, an oxidant-sensitive fluorescent probe, we did not find significant age-or vessel-related differences in O 2 Successful adaptation of the newborn to postnatal conditions requires a dramatic transition of the pulmonary circulation from a high-resistance state in utero to a low-resistance state within minutes after birth. Some infants fail to achieve or sustain this normal decrease in pulmonary vascular resistance, which leads to severe respiratory distress and hypoxemia, referred to as PPHN (1) NO ⅐ , a free radical species produced by a wide variety of cell types, has gained recognition as a key mediator of diverse physiologic and pathologic processes, including the regulation of pulmonary vascular tone and the perinatal adaptation of the lung circulation (1).

Pulmonary Arterial Contractility in Neonatal Lambs Increases with 100% Oxygen Resuscitation

“…Many laboratories (including ours) that study isolated vessels in conventional tissue baths use a 94% oxygen and 6% CO 2 gas mixture (8,23,24). The PO 2 of the buffer solution bathing the tissue is close to 500 mm Hg and PCO 2 is approximately 40 mm Hg.…”

Effects of Lipid Formulations of Amphotericin B on Activity of Human Monocytes against Aspergillus fumigatus

“…In contrast to the O 2 Ϫ response, there was an increase in the production of H 2 O 2 and secondary DIIs from MNCs pre- (23).…”

Age-Related Differences in Vasoconstrictor Responses to Isoprostanes in Piglet Pulmonary and Mesenteric Vascular Smooth Muscle

“…The isometric force signal was amplified, A/D converted (PowerLab, ADInstruments Pty., Castle Hill, Australia), and recorded (Chart v3.4, ADInstruments Pty.). An optimal resting tension of 0.3 g (PA of 12-to 24 h-old animals), 0.5 g (PA of 2-wk-old animals and PV of both groups), 1 g (MA of 12-to 24 h-old animals), or 2 g (MA of 2-wk-old animals) was applied to the vascular segments, as determined from previous experiments (14,15). Tissues were allowed to equilibrate for 60 -90 min.…”

“…Pulmonary veins are exposed to higher oxygen concentrations than PA, but it seems that this fact does not imply a higher activity of antioxidant defenses (15,31). Thus, PV are presumably exposed to higher oxidant conditions and, consequently, to higher formation of isoprostanes.…”

“…An increasing body of evidence seems to indicate that free radicals are involved in several neonatal disease processes such as chronic lung disease, retinopathy of prematurity, necrotizing enterocolitis, and periventricular leukomalacia (12,36). There are also accumulating data implying the involvement of reactive oxygen species and oxidative stress in signal transduction of numerous biologic processes, including control of newborn transitional circulation (15,16,37). This type of cell signalling consistently implies the additional involvement of other bioactive molecules, such as isoprostanes, that stem from reactive oxygen species reaction with cell membrane lipids.…”