Intrauterine growth restriction is associated with sex-specific alterations in the nitric oxide/cyclic GMP relaxing pathway in the human umbilical vein.
Placenta
; 93: 83-93, 2020 04.
Article
in En
| MEDLINE
| ID: mdl-32250743
ABSTRACT
INTRODUCTION:
Intrauterine growth restriction (IUGR) is a leading cause of perinatal mortality and morbidity, and is linked to an increased risk to develop chronic diseases in adulthood. We previously demonstrated that IUGR is associated, in female neonates, with a decreased nitric oxide (NO)-induced relaxation of the umbilical vein (UV). The present study aimed to investigate the contribution of the smooth muscle components of the NO/cyclic GMP (cGMP) pathway to this alteration.METHODS:
UVs were collected in growth-restricted or appropriate for gestational age (AGA) human term newborns. Soluble guanylyl cyclase (sGC) and cGMP-dependent protein kinase (PKG) were studied by Western blot, cGMP production by ELISA and cyclic nucleotide phosphodiesterases (PDEs) activity using a colorimetric assay. Contribution of PDEs was evaluated using the non-specific PDEs inhibitor 3-isobutyl-1-methylxanthine (IBMX) in isolated vessel tension studies.RESULTS:
NO-induced relaxation was reduced in IUGR females despite increased sGC protein and activity, and some increase in PKG protein compared to AGA. In males, no significant difference was observed between both groups. In the presence of IBMX, NO-stimulated cGMP production was significantly higher in IUGR than AGA females. Pre-incubation with IBMX significantly improved NO-induced relaxation in all groups and abolished the difference between IUGR and AGA females.CONCLUSION:
IUGR is associated with sex-specific alterations in the UV's smooth muscle. The impaired NO-induced relaxation observed in growth-restricted females is linked to an imbalance in the NO/cGMP pathway. The beneficial effects of IBMX suggest that PDEs are implicated in such alteration and they could represent promising targets for therapeutic intervention.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Umbilical Veins
/
Sex Characteristics
/
Cyclic GMP
/
Fetal Growth Retardation
/
Nitric Oxide
Type of study:
Observational_studies
/
Risk_factors_studies
Limits:
Adult
/
Female
/
Humans
/
Male
/
Newborn
/
Pregnancy
Language:
En
Journal:
Placenta
Year:
2020
Document type:
Article
Publication country:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS