Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019270 (hernia)
 15,856 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital diaphragmatic hernia (CDH) is a major cause of refractory respiratory failure in the neonatal period and is characterized by persistent pulmonary hypertension of the newborn (PPHN) and pulmonary hypoplasia. Endothelin-1 (ET-1) dysregulation may play a significant role in the pathophysiology of PPHN and ET-1 acts through binding to type A (ETA) and type B (ETB) receptors. Therefore, ETA and ETB receptor protein expression was studied using immunohistochemistry in 10 lung specimens obtained from newborns with CDH, and 4 normal lung specimens, in order to explore whether dysregulation of ETA and ETB expression contributes to PPHN. ETA and ETB mRNAs were then quantified using real-time RT-PCR in laser-microdissected pulmonary resistive arteries. In the lungs of newborns with CDH, immunohistochemistry of both ETA and ETB receptors demonstrated over-expression in the thickened media of pulmonary arteries. Using laser microdissection and real-time RT-PCR, higher levels of ETA and ETB mRNA were found in CDH pulmonary arteries than in controls: this increase was more pronounced for ETA mRNA. This study provides the first demonstration of ET-1 receptor dysregulation in association with structural alteration of pulmonary arteries in newborns with CDH and PPHN. This dysregulation preferentially affects the ETA receptor. These results suggest that dysregulation of ET-1 receptors may contribute to PPHN associated with CDH.
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PMID:Endothelin receptor expression in human lungs of newborns with congenital diaphragmatic hernia. 1554 26

The high mortality in patients with congenital diaphragmatic hernia (CDH) has been attributed to pulmonary hypoplasia and persistent pulmonary hypertension (PPH). Endothelin-1 (ET-1), nitric oxide (NO), and calcitonin gene-related peptide (CGRP) have been reported to be important vasoactive mediators in the perinatal pulmonary circulation. The exact mechanism by which these vasoactive mediators interact to regulate the perinatal pulmonary vascular tone in CDH with PPH is not fully understood. We hypothesized that the altered pulmonary vascular reactivity in CDH is due to imbalance in vasoactive mediators. This study was designed to investigate mRNA expression of ET-1, eNOS, and CGRP in CDH lung in the perinatal period. A CDH model was induced in pregnant rats following administration of nitrofen. In control animals, the same dose of olive oil was given without nitrofen. Cesarean section was performed on day 21 of gestation. The newborn rats were intubated and ventilated, and ventilation was continued for 1-6 h. Left lungs were collected from both groups at 0, 1, and 6 h after ventilation (n=8 in each group). Reverse transcriptase-polymerase chain reaction on lung tissue was performed to evaluate the relative level of ET-1, eNOS, and CGRP mRNA expression. The results showed a significant increase in ET-1 mRNA in CDH lung at 1 and 6 h after ventilation compared with controls. In CDH lung, eNOS mRNA and CGRP mRNA levels were significantly increased at 1 h but were similar to control values at 6 h after ventilation. The increased expression of vasoconstrictor ET-1 mRNA and vasodilators eNOS mRNA and CGRP mRNA in the CDH lung at 1 h after ventilation suggests that pulmonary vascular tone is rapidly changing after birth. An imbalance in the production of vasoconstrictors and vasodilators by the CDH lung may contribute to high pulmonary vascular resistance.
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PMID:Expression of vasoactive mediators during mechanical ventilation in nitrofen-induced diaphragmatic hernia in rats. 1575 63