Altered regulation of natriuretic peptides in the rat heart by prenatal exposure to morphine

Abstract

Both endogenous and exogenous opioids modulate blood pressure and cardiac function by stimulating cardiac synthesis of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP). Since morphine crosses the placental barrier, it could alter the ANF‐BNP system in the fetal heart. The aim of this study was to characterize cardiac natriuretic peptides in normal rat development and in rats prenatally exposed to morphine. Female rats received either saline or morphine (10 or 20 mg kg−1 day−1) via osmotic minipumps during gestation. The effects of this treatment were investigated in offspring at 1, 4 and 22 days of age. During maturation, atrial ANF and ANF mRNA increased by 3‐fold from birth to 3 weeks of age, but BNP and BNP mRNA tended to decrease. In the ventricles, both ANF and BNP content decreased at 3 weeks after birth, from 25.11 ± 3.6 to 0.81 ± 0.1 ng (P < 0.001), and from 3.36 ± 0.33 to 0.19 ± 0.01 ng (P < 0.001), respectively. However, whereas ventricular ANF mRNA decreased, BNP mRNA levels did not change during maturation. Prenatal exposure to morphine significantly increased ANF content in the left atria of 22‐day‐old rats, and in the right atria of 1‐, 4‐ and 22‐day‐old rats compared with age‐matched saline controls. In contrast, prenatal exposure to 20 mg kg−1 day−1 morphine significantly inhibited BNP and BNP mRNA in the ventricles at all ages studied. These observations suggest that alterations in mRNA synthesis or stability and/or post‐translational processing of ANF and BNP occur in the heart during maturation, and that prenatal exposure to morphine alters cardiac production, and possibly release, of both peptides.

Biomimetic engineering of the cardiac tissue through processing, functionalization, and biological characterization of polyester urethanes

“…Moreover, for the first time a modulation of CNP, which expression reflects those of BNP, was observed, underlining that during cardiomyocyte maturation NPs are modified in a different manner. These results are in line with a previous study where it was hypothesized that their trend during phenotype differentiation is probably caused by differences in sequence genes, rate of transcription and differential stabilization of the mRNA [49].…”

Natriuretic peptide system in fetal heart and circulation

“…Whereas an increase in both ANP and BNP in the heart of fetal rats, induced by maternal diabetes [36], demonstrates similar regulation cascades for their gene expression, the observation that prenatal exposure to morphine induces an up-regulation of cardiac ANP and a down-regulation of BNP [12] indicates a bifunctional importance of the system in the fetal heart and circulation.…”

“…In contrast to the atria, in which BNP and BNP mRNA decline with advancing gestational age, in cardiac ventricles only the peptide decreases, BNP mRNA remaining unchanged [12]. This could be explained by an altered posttranslational processing of ANP and BNP during heart maturation, or an increase in neutral endopeptidase EC 3.4.24.11 (NEP) activity, as NEP is the main catabolic enzyme for both natriuretic peptides.…”

Functional changes after prenatal opiate exposure related to opiate receptors' regulated alterations in cholinergic innervation

“…This was done from necessity because multiple daily injections which best simulate the drug addiction situation would be too stressful to the mouse, potentially inducing confounding indirect effects that would result in an unacceptable rate of fetal death. Administration of neuroteratogens, including opioids, via osmotic minipumps was carried out by several groups to minimize the indirect effects of the neuroteratogens and to moderate the peaks and valleys of drug levels (Ernest et al, 1998;Robinson et al, 1997;Slotkin, 1998). While the advantages of this procedure are obvious, we still chose to deliver the drug by injection which better simulates the situation in the addicted mother.…”