Premature babies often require oxygen therapy for preventing brain damage. Unfortunately, excessive oxygen supply can damage immature lungs and lead to severe life-long illnesses including bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH).
A recent study revealed that important role of adrenomedullin hormone in the development, recovery and prevention form PH and BPD.
The study findings are published in the American Journal of Pathology.
Bronchopulmonary dysplasia (BPD) is a lung disease caused by the reduced growth rate of lung frequently occurs in the prematurely born babies. In the United States, it affects 10,000 neonates every year. It is the second most expensive disease among children. Oxygen therapy elevates BPD risks. Babies having BPD may develop asthma, physical or mental disabilities and lung infections.
The professor at the Baylor College of Medicine, Binoy Shivana said that the findings of this study provide proved that adrenomedullin influence the progression and the resolution of experimental BPD and PH by affecting lung vascular health. Importantly, there is not any cure for BPD, however, study findings suggest that adrenomedullin can be used as a therapy for reducing the burden of BPD –associated PH in the premature babies.
Though adrenomedullin helps in repairing damaged lung, blood vessels and heart in older age human, rats and mice but its role in resolving experimental BPD-linked PH are not clear.
For understanding this role, investigators studied lung function and structure in newborn mice who were genetically bred to have lower levels of adrenomedullin than normal and compared them with those having normal levels. The exposed one-day-old mice to both normal and increased concentrations of oxygen for 14 consecutive days. Lung structure, including several blood vessels and markers of cell damage, was examined at different times up to 28 days. The heart was also examined for pulmonary hypertension by imaging on day 28 and 70.
The study observed that newborn mice who were deficient in adrenomedullin exposed to high oxygen levels were more likely to have damaged lung. They had greater cell death, fewer blood vessels and alveoli in lung and had more severe signs and symptoms of BPD and PH from which they recover slowly as compared to the mice with normal adrenomedullin levels. This concludes that adrenomedullin is essential for normal development of the lungs.
The mice who were adrenomedullin-deficient also showed fewer levels of enzyme endothelial nitric oxide synthase (eNOS) which indicates that adrenomedullin may mediate its effect via eNOS.
The investigators looked at the effect of hormone adrenomedullin in endothelial cells of the human lung. Dr Shivanna said that they found blocking this hormone of its receptors decreased the expression of the eNOS enzyme. While on the other hand, adrenomedullin therapy increased the cell ability to form blood vessels, and this ability of adrenomedullin was lost when the function of eNOS was blocked by the genetic manipulation.
Dr Shivanna believes that adrenomedullin hormone could be the novel therapeutic target for treating BPD-associated PH in premature babies. This is normally produced hormone in the body so this hormonal therapy can be safe without adverse effects.
The study showed that adrenomedullin hormone may improve the life quality of BPD-associated PH patients with its long-lasting beneficial effects on the heart and lungs.