Mechanisms of vascular dysfunction in the interleukin-10-deficient murine model of preeclampsia indicate nitric oxide dysregulation.
Kidney Int
; 99(3): 646-656, 2021 03.
Article
in En
| MEDLINE
| ID: mdl-33144212
ABSTRACT
Preeclampsia is a pregnancy-specific hypertensive disorder characterized by proteinuria, and vascular injury in the second half of pregnancy. We hypothesized that endothelium-dependent vascular dysfunction is present in a murine model of preeclampsia based on administration of human preeclamptic sera to interleukin-10-/- mice and studied mechanisms that underlie vascular injury. Pregnant wild type and IL-10-/- mice were injected with either normotensive or severe preeclamptic patient sera (sPE) during gestation. A preeclampsia-like phenotype was confirmed by blood pressure measurements; assessment of albuminuria; measurement of angiogenic factors; demonstration of foot process effacement and endotheliosis in kidney sections; and by accumulation of glycogen in placentas from IL-10-/- mice injected with sPE sera (IL-10-/-sPE). Vasomotor function of isolated aortas was assessed. The IL-10-/-sPE murine model demonstrated significantly augmented aortic contractions to phenylephrine and both impaired endothelium-dependent and, to a lesser extent, endothelium-independent relaxation compared to wild type normotensive mice. Treatment of isolated aortas with indomethacin, a cyclooxygenase inhibitor, improved, but failed to normalize contraction to phenylephrine to that of wild type normotensive mice, suggesting the additional contribution from nitric oxide downregulation and effects of indomethacin-resistant vasoconstricting factors. In contrast, indomethacin normalized relaxation of aortas derived from IL-10-/-sPE mice. Thus, our results identify the role of IL-10 deficiency in dysregulation of the cyclooxygenase pathway and vascular dysfunction in the IL-10-/-sPE murine model of preeclampsia and point towards a possible contribution of nitric oxide dysregulation. These compounds and related mechanisms may serve both as diagnostic markers and therapeutic targets for preventive and treatment strategies in preeclampsia.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pre-Eclampsia
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
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Humans
/
Pregnancy
Language:
En
Journal:
Kidney Int
Year:
2021
Type:
Article
Affiliation country:
United States