vasoactive-intestinal-peptide and Bronchopulmonary-Dysplasia

The use of oxygen therapy (high doses of oxygen - hyperoxia) in the treatment of premature infants results in their survival. However, it also results in a high incidence of chronic lung disease known as bronchopulmonary dysplasia, a disease in which airway hyper-responsiveness and pulmonary hypertension are well known as consequences. In our previous studies, we have shown that hyperoxia causes airway hyper-reactivity, characterized by an increased constrictive and impaired airway smooth muscle relaxation due to a reduced release of relaxant molecules such as nitric oxide, measured under in vivo and in vitro conditions (extra- and intrapulmonary) airways. In addition, the relaxation pathway of the vasoactive intestinal peptide (VIP) and/or pituitary adenylate cyclase activating peptide (PACAP) is another part of this system that plays an important role in the airway caliber. Peptide, which activates VIP cyclase and pituitary adenylate cyclase, has prolonged airway smooth muscle activity. It has long been known that VIP inhibits airway smooth muscle cell proliferation in a mouse model of asthma, but there is no data about its role in the regulation of airway and tracheal smooth muscle contractility during hyperoxic exposure of preterm newborns.

Topics: Airway Remodeling; Animals; Animals, Newborn; Bronchopulmonary Dysplasia; Disease Models, Animal; Gestational Age; Humans; Hyperoxia; Infant, Newborn; Infant, Premature; Lung; Muscle, Smooth; Oxygen Inhalation Therapy; Pituitary Adenylate Cyclase-Activating Polypeptide; Premature Birth; Signal Transduction; Vasoactive Intestinal Peptide

A total of ten 6-month-old male rhesus monkey (Macaca mulatta) infants, born full-term, were positive-pressure ventilated with greater than 95% oxygen or room air (controls). A protocol was used which closely simulated pediatric intensive care. To test if regulatory peptides were affected by the oxygen treatment, and to search for an early marker of oxygen toxicity, lung tissue samples and systemic mixed venous blood were collected at 6, 12 and 24 hours after onset of treatment. The peptides, gastrin releasing peptide (GRP), calcitonin gene-related peptide (CGRP), peptide YY (PYY), vasoactive intestinal peptide (VIP) and somatostatin (SOM), were quantitated in lung tissue extracts and plasma using radioimmunoassay. Lung tissue GRP, CGRP, and PYY levels appeared to decrease gradually with time, perhaps as a result of the positive pressure ventilation procedure. GRP and CGRP levels decreased less among monkey infants ventilated with oxygen, thus they were significantly higher at 24 hours than in air ventilated controls. VIP levels were significantly lower among tests compared to controls at that time. Blood peptide levels did not change with oxygen treatment. These results suggest that tissue concentrations of certain pulmonary regulatory peptides can become altered by ventilation with greater than 95% oxygen. A blood borne peptide marker was not identified.

Topics: Animals; Animals, Newborn; Bronchopulmonary Dysplasia; Gastrin-Releasing Peptide; Humans; Infant, Newborn; Lung; Macaca mulatta; Male; Oxygen Inhalation Therapy; Peptide YY; Peptides; Radioimmunoassay; Somatostatin; Vasoactive Intestinal Peptide