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

  • Pediatr Res. 2020 May;87(6):991-997. doi: 10.1038/s41390-019-0716-x.
Stacey L Crockett  1 ,  Micah Harris  1 ,  Naoko Boatwright  1 ,  Rachel L Su  1 ,  Michael T Yarboro  2 ,  Courtney D Berger  1 ,  Elaine L Shelton  1  3 ,  Jeff Reese   #  1  2 ,  Jeffrey L Segar   #  4
Affiliations
  • 1. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.
  • 2. Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.
  • 3. Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
  • 4. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA. [email protected].
  • # Contributed equally.
PMID: 31816622 DOI: 10.1038/s41390-019-0716-x
Abstract

Background: Indomethacin treatment for patent ductus arteriosus (PDA) is associated with acute kidney injury (AKI). Fenoldopam, a dopamine (DA) DA1-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 (DA1-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: DA1 receptors were expressed equally in ductus and aorta. High-dose DA induced modest vasoconstriction under newborn O2 conditions. Phentolamine inhibited DA-induced constriction, while SCH23390 augmented constriction, consistent with a vasodilatory role for DA1 receptors. Despite this, fenoldopam had little effect on ductus tone nor indomethacin- or O2-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 DA1-mediated impairment of ductus closure supports the study of potential role for fenoldopam during PDA treatment.

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