Age dependency of vasopressin pulmonary vasodilatory effect in rats

BACKGROUND: Vasopressin is a systemic vasoconstrictor. Its pulmonary vasodilatory effect is controversial, and limited data are available on its use in neonates with pulmonary hypertension. Hypothesizing that the vasopressin-induced pulmonary vasodilation is developmentally regulated, we evaluated its pulmonary and systemic arterial response in newborn and adult rats. METHODS: Vessels were mounted on a wire myograph, and the vasopressin-induced changes in vasomotor tone measured. The vessel-and age-dependent differences in vasopressin V-1a and V-2 receptors' expression were evaluated by western blotting. RESULTS: Vasopressin induced a dose-dependent increase in mesenteric arterial tone at both ages, but of greater magnitude in adult vessels (P < 0.01). At lower concentrations, vasopressin induced pulmonary vasodilation in adult vessels and vasoconstriction in newborn arteries. The adult vasopressin-induced pulmonary vasodilation was inhibited by ibuprofen, suggesting that the response is prostaglandin mediated. Pulmonary tissue V-1a receptor protein expression was higher in adult, when compared with newborn arteries (P < 0.01). The adult vessels V-1a expression predominated in the pulmonary arteries, and V-2 was only detected in mesenteric arteries. CONCLUSION: The vasopressin-induced pulmonary vasodilation is absent in newborn rats likely due to the lower tissue V-1a expression early in life. These animal data challenge the therapeutic use of vasopressin in neonatal pulmonary hypertension.