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

Abstract

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 (αadrenergic 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 2induced constriction and did not impair postnatal closure in vivo. Conclusion(s): DA receptors are present in the ductus but have limited physiologic effects. DAinduced ductus vasoconstriction is mediated via α-adrenergic pathways. The absence of DA 1-Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Prdm6 drives ductus arteriosus closure by promoting ductus arteriosus smooth muscle cell identity and contractility

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