Congenital diaphragmatic hernia (CDH) with its associated pulmonary hypoplasia and pulmonary hypertension carries a 40-50% mortality rate which has not changed in recent years despite aggressive therapeutic modalities. In the canine lung, catecholamine stimulation increased pulmonary vascular resistance and decreased pulmonary vascular compliance by means of alpha-1 and alpha-2 receptor interaction with beta-2 receptors. After pulmonary vasoconstriction, this response to catecholamines was not present possibly secondary to an increase in the beta-2 vasodilatory response and a decrease in the alpha vasoconstrictive response. Since the pathology in the nitrofen induced animal model of CDH mirrors that seen in the human, it makes a good model for studying the role of receptors in the pathophysiology of CDH.

We investigated alpha and beta adrenergic receptor expression in the lungs of normal and CDH rats. To induce CDH, pregnant rats received 100mg orally of nitrofen on day 10 of gestation. This is known to induce a left-sided or bilateral defect in 70-90% of the offspring. Offspring of non-treated mothers served as controls. In situ hybridization was performed using oligonucleotide probes specific for the alpha-1D, alpha-1B, alpha-2C10, alpha-2C4, beta-1 and beta-2 subtypes. The beta-2 subtype showed approximately a 50% increase in expression in the CDH versus control animals. Smaller increases in the alpha-1B and beta-2 subtypes were also observed.

Alterations in adrenergic receptor expression may contribute to the pathophysiology observed in CDH. These results may help explain the physiologic increase in beta-2 response to catecholamines in the canine model of pulmonary vasoconstriction.