Role of dopamine and selective dopamine receptor agonists on mouse ductus arteriosus tone and responsiveness

BACKGROUND: Indomethacin treatment for patent ductus arteriosus (PDA) is associated with acute kidney injury (AKI). Fenoldopam, a dopamine (DA) DA(1)-like receptor agonist dilates the renal vasculature and may preserve renal function during indomethacin treatment. However, limited information exists on DA receptor-mediated signaling in the ductus and fenoldopam may prevent ductus closure given its vasodilatory nature. METHODS: DA receptor expression in CD-1 mouse vessels was analyzed by qPCR and immunohistochemistry. Concentration-response curves were established using pressure myography. Pretreatment with SCH23390 (DA(1)-like receptor antagonist), phentolamine (α - adrenergic receptor antagonist) or indomethacin addressed mechanisms for DA-induced changes. Fenoldopam’s effects on postnatal ductus closure were evaluated in vivo. RESULTS: DA(1) receptors were expressed equally in ductus and aorta. High-dose DA induced modest vasoconstriction under newborn O(2) conditions. Phentolamine inhibited DA-induced constriction, while SCH23390 augmented constriction, consistent with a vasodilatory role for DA(1) receptors. Despite this, fenoldopam had little effect on ductus tone nor indomethacin- or O(2)-induced constriction and did not impair postnatal closure in vivo. CONCLUSION(S): DA receptors are present in the ductus but have limited physiologic effects. DA-induced ductus vasoconstriction is mediated via α-adrenergic pathways. The absence of DA(1)-mediated impairment of ductus closure supports the study of potential role for fenoldopam during PDA treatment.