Expression of Adrenoceptor Subtypes in Preterm Piglet Heart Is Different to Term Heart

Min Young Kim,Yvonne A Eiby,Barbara E Lingwood,Eugenie R Lumbers,Karen J Gibson,Angela M Finch,Amanda C Boyce,Katherine Yutzey

doi:10.1371/journal.pone.0092167

Min Young Kim, Yvonne A Eiby + Show 6 more

Open Access

https://doi.org/10.1371/journal.pone.0092167

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Abstract

Preterm delivery increases the risk of inadequate systemic blood flow and hypotension, and many preterm infants fail to respond to conventional inotrope treatments. If the profile of cardiac adrenoceptor subtypes in the preterm neonate is different to that at term this may contribute to these clinical problems. This study measured mRNA expression of β1, β2, α1A, α2A and α2B-adrenoceptor subtypes by real time PCR in term (113d), preterm (91d) and preterm piglets (91d) exposed to maternal glucocorticoid treatment. Abundance of β-adrenoceptor binding sites in the left ventricle was measured using saturation binding assays. Relative abundance of β1-adrenoceptor mRNA in untreated preterm hearts was ∼50% of term abundance in both left and right ventricles (P<0.001). Trends in receptor binding site density measurements supported this observation (P = 0.07). Glucocorticoid exposure increased β1-adrenoceptor mRNA levels in the right ventricle of preterm hearts (P = 0.008) but did not alter expression in the left ventricle (P>0.1). Relative abundance of α1A-adrenoceptor mRNA was the same in preterm and term piglet hearts (P = >0.1) but was reduced by maternal glucocorticoid treatment (P<0.01); α2A-adrenoceptor mRNA abundance was higher in untreated and glucocorticoid exposed preterm piglet hearts than in term piglets (P<0.001). There was no difference between male and female piglets in mRNA abundance of any of the genes studied. In conclusion, there is reduced mRNA abundance of β1-adrenoceptors in the preterm pig heart. If this lower expression of β-adrenoceptors occurs in human preterm infants, it could explain their poor cardiovascular function and their frequent failure to respond to commonly used inotropes.

Highlights

Following preterm birth, many neonates exhibit low systemic blood flow (SBF) and/or hypotension [1], and this is associated with an increased risk of infant morbidity and mortality [2,3,4]
There is evidence suggesting that the profile of adrenoceptor subtypes in the heart changes with development [6,7,8,9,10,11], and it is acknowledged that the preterm infant may have a reduced number of b-adrenoceptors [2,12]
There are no studies covering the preterm period in large animals with a similar degree of cardiac maturation at birth to that of the human infant. As adrenergic agonists such as dopamine and dobutamine continue to be a mainstay in the treatment of preterm infants with cardiovascular compromise, it is essential that we understand the profile of adrenoceptor expression prior to term

Summary

Introduction

Many neonates exhibit low systemic blood flow (SBF) and/or hypotension [1], and this is associated with an increased risk of infant morbidity and mortality [2,3,4]. We tested these hypotheses by measuring the mRNA abundance of the subtypes of the a- and b-adrenoceptors, and by using saturation binding assays to measure the number of b-adrenoceptors on cardiac membranes isolated from male and female preterm and term piglets, and from male and female preterm piglets exposed to maternally administered glucocorticoids.

Results

Conclusion