Expression of vasoactive mediators during mechanical ventilation in nitrofen-induced diaphragmatic hernia in rats
- 98 Downloads
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.
KeywordsPersistent pulmonary hypertension (PPH) Congenital diaphragmatic hernia (CDH) Endothelin-1 (ET-1) Nitric oxide (NO) Calcitonin gene-related peptide (CGRP)
- 1.Puri P (1994) Congenital diaphragmatic hernia. Curr Prob Surg 31:785–859Google Scholar
- 5.Belik J, Halayko AJ, Rao K, Stephens NL (1993) Fetal ductus arteriosus ligation. Pulmonary vascular smooth muscle biochemical changes. Cric Res 72:588–596Google Scholar
- 9.North AJ, Moya FR, Mysore MR, Thomas VL, Wells LB, Wu LC, Shaul PW (1995) Pulmonary endothelial nitric oxide synthase gene expression is decreased in a rat model of congenital diaphragmatic hernia. Am J Respir Cell Molk Biol 13:676–682Google Scholar