RESUMEN
Precapillary arteries constrict during alveolar hypoxia in a response known as hypoxic pulmonary vasoconstriction (HPV). The mechanism by which pulmonary arterial smooth muscle cells (PASMCs) detect a decrease in Po(2) and trigger contraction is not fully understood. Previous studies in cultured PASMCs show that hypoxia induces an increase in reactive oxygen species (ROS) production, but these results may not reflect responses of PASMCs in their native tissue environment. We therefore assessed hypoxia-induced changes in cytosolic ROS in PASMCs of precision-cut mouse lung slices expressing the redox-sensitive protein, RoGFP. Superfusion of lung slices with hypoxic media (1.5% O(2)) resulted in a significant oxidation of RoGFP from normoxic baseline that was attenuated by overexpression of cytosolic catalase. Hypoxic superfusion also increased [Ca(2+)](i) above normoxic baseline; this response was significantly attenuated by cytosolic catalase overexpression or by the administration of EUK134, a synthetic SOD-catalase mimetic. The hypoxia-induced increase in [Ca(2+)](i) was abolished in the absence of extracellular Ca(2+), indicating that ROS signals trigger entry of extracellular calcium. Collectively, these results indicate that an increase in cytosolic ROS signaling is required for the increase in [Ca(2+)](i) in PASMCs in precision-cut mouse lung slices during the acute HPV response.
Asunto(s)
Calcio/metabolismo , Hipoxia/metabolismo , Miocitos del Músculo Liso/metabolismo , Arteria Pulmonar/citología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/fisiología , Animales , Células Cultivadas , Colorantes Fluorescentes/metabolismo , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Pulmón/irrigación sanguínea , Pulmón/citología , Pulmón/metabolismo , Ratones , Músculo Liso Vascular/citología , Miocitos del Músculo Liso/citología , Oxidación-ReducciónRESUMEN
In perinatal epidemiology, transgenerational risk factors are defined as conditions experienced by one generation that affect the pregnancy outcomes of the next generation. The authors investigated the transgenerational effect of neighborhood poverty on infant birth weight among African Americans. Stratified and multilevel logistic regression analyses were performed on an Illinois transgenerational data set with appended US Census income information. Singleton African-American infants (n = 40,648) born in 1989-1991 were considered index births. The mothers of index infants had been born in 1956-1976. The maternal grandmothers of index infants were identified. Rates of infant low birth weight (<2,500 g) rose as maternal grandmother's residential environment during her pregnancy deteriorated, independently of mother's residential environment during her pregnancy. In a multilevel logistic regression model that accounted for clustering by maternal grandmother's residential environment, the adjusted odds ratio (controlling for mother's age, education, prenatal care, cigarette smoking status, and residential environment) for infant low birth weight for maternal grandmother's residence in a poor neighborhood (compared with an affluent neighborhood) equaled 1.3 (95% confidence interval: 1.1, 1.4). This study suggests that maternal grandmother's exposure to neighborhood poverty during her pregnancy is a risk factor for infant low birth weight among African Americans.