Authors: Toko Shinkai Hideki Shima Valeria Solari Prem Puri
Publish Date: 2004/11/26
Volume: 21, Issue: 3, Pages: 143-147
Abstract
The high mortality in patients with congenital diaphragmatic hernia CDH has been attributed to pulmonary hypoplasia and persistent pulmonary hypertension PPH Endothelin1 ET1 nitric oxide NO and calcitonin generelated 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 ET1 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 transcriptasepolymerase chain reaction on lung tissue was performed to evaluate the relative level of ET1 eNOS and CGRP mRNA expression The results showed a significant increase in ET1 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 ET1 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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