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.