Recovery from withdrawal of inhaled nitric oxide and kinetics of nitric oxide-induced inhibition of nitric oxide synthase activity in vitro. 2000

J Dötsch, and S Demirakça, and K Zepf, and J Hänze, and S Parida, and W Rascher
Department of Pediatrics, Friedrich-Alexander University of Erlangen-Nürnberg, Germany. JoergWDoetsch@yahoo.com

OBJECTIVE To examine the kinetics of successful nitric oxide (NO) withdrawal in vivo and in vitro. METHODS Prospective study in a university pediatric intensive care ward and research laboratory. METHODS Nineteen patients with acute respiratory distress syndrome (ARDS) or persistent pulmonary hypertension of the newborn (PPHN). Primary porcine pulmonary artery cells in vitro. METHODS NO inhalation and withdrawal in patients; exposure to NO donor sodium nitroprusside (SNP) and gaseous NO in vitro. RESULTS In patients: a slight, but significant, increase of oxygenation index (OI) from 4.57 +/- 0.24 cmH2O/torr (mean +/- SEM) to 4.90 +/- 0.26 cmH2O/torr after withdrawal of NO (p < 0.001). Recovery of OI (4.43 +/- 0.23 cmH2O/torr) 30 min after weaning, a significant drop after 4 h (3.72 +/- 0.17 cmH2O/ torr;p < 0.001), values restored after 12 h. In vitro: NO synthase (NOS) activity was significantly lower in SNP-incubated cells (20.0 +/- 4.0 microM/min) than in control cells (37.6 +/- 7.0 microM/ min; p < 0.05). Thirty minutes after SNP withdrawal there was NOS activity of 35.8 +/- 10.0 microM/min with a significant increase by 4 h (p < 0.05). No alteration of endothelial NOS (ENOS) mRNA expression by NO (Northern Blot). CONCLUSIONS In patients there is a slight, but significant, reversible increase of OI after successful weaning from NO. In vitro, NO leads to a reversible decrease of ENOS activity on a post mRNA level, resembling clinical observations.

UI MeSH Term Description Entries
D006976 Hypertension, Pulmonary Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES. Pulmonary Hypertension
D007223 Infant A child between 1 and 23 months of age. Infants
D007231 Infant, Newborn An infant during the first 28 days after birth. Neonate,Newborns,Infants, Newborn,Neonates,Newborn,Newborn Infant,Newborn Infants
D008297 Male Males
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D011446 Prospective Studies Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. Prospective Study,Studies, Prospective,Study, Prospective
D012127 Respiratory Distress Syndrome, Newborn A condition of the newborn marked by DYSPNEA with CYANOSIS, heralded by such prodromal signs as dilatation of the alae nasi, expiratory grunt, and retraction of the suprasternal notch or costal margins, mostly frequently occurring in premature infants, children of diabetic mothers, and infants delivered by cesarean section, and sometimes with no apparent predisposing cause. Infantile Respiratory Distress Syndrome,Neonatal Respiratory Distress Syndrome,Respiratory Distress Syndrome, Infant
D001993 Bronchodilator Agents Agents that cause an increase in the expansion of a bronchus or bronchial tubes. Bronchial-Dilating Agents,Bronchodilator,Bronchodilator Agent,Broncholytic Agent,Bronchodilator Effect,Bronchodilator Effects,Bronchodilators,Broncholytic Agents,Broncholytic Effect,Broncholytic Effects,Agent, Bronchodilator,Agent, Broncholytic,Agents, Bronchial-Dilating,Agents, Bronchodilator,Agents, Broncholytic,Bronchial Dilating Agents,Effect, Bronchodilator,Effect, Broncholytic,Effects, Bronchodilator,Effects, Broncholytic
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children

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