Although dexamethasone has been used to treat the severe hypotension in extremely low birth weight infants, the mechanism of action of dexamethasone is unknown. Previously we observed an increase in carotid artery contractile response to al-adrenergic agonists over the first two weeks of life in rats. We also observed that dexamethasone enhances maturation of α1-adrenergic mediated vessel contraction in 3-5 day old rats. In this study we tested the hypothesis that dexamethasone enhances α1-adrenergic receptor response by suppression of nitric oxide synthase production. Pups were treated with SC dexamethasone 0.4μg/gm body weight or saline from DOL 2 until sacrifice. Carotid arteries were isolated and vessel responses were studied in a myograph. The results in the table below represent maximum percent decrease in vessel diameter in reponse to phenylephrine (PE) in the presence or absence of L-NAME. Data were analyzed by Student's t test. In separate experiments, carotid arteries from dexamethasone and control rats were isolated for nitric oxide synthase mRNA expression. There was no difference in inducible or endothelial nitric oxide synthase expression in control vs. dexamethasone treated rats. These results indicate there is nitric oxide production in these vessels, which when inhibited by L-NAME allows greater contraction to the α1-adrenergic agonist phenylephrine. Although dexamethasone enhances α1-adrenergic contractile response in vessels from first week of life animals, the action of dexamethasone in these vessels does not appear to be related to downregulation of nitric oxide synthase mRNA expression.

Table 1
Full size table