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Role of dopamine and selective dopamine receptor agonists on mouse ductus arteriosus tone and responsiveness. Pediatr Res 2020 05;87(6):991-997

Date

12/10/2019

Pubmed ID

31816622

Pubmed Central ID

PMC7196482

DOI

10.1038/s41390-019-0716-x

Scopus ID

2-s2.0-85076889181

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.

Author List

Crockett SL, Harris M, Boatwright N, Su RL, Yarboro MT, Berger CD, Shelton EL, Reese J, Segar JL

Author

Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin




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