The effects of hypertensive disorders of pregnancy (HDP) on resistance arteries after postpartum in an experimental rat model [EMBARGOED]

Abstract

Hypertensive disorders of pregnancy (HDPs) contribute to a significant percentage of maternal and foetal morbidity and mortality worldwide. Despite the normalisation of blood pressure postpartum, women with a history of HDPs have an increased two-to-four-fold risk of developing cardiovascular diseases (CVDs) later in life. One of the aetiologies of CVDs is endothelial dysfunction. We hypothesised that the transient high blood pressure during HDPs leads to persistent and ongoing endothelial dysfunction (ED) and, ultimately, the development of CVDs in women. This study aimed to explore the effects of high blood pressure during pregnancy through histopathological, biochemical, immunohistochemical (IHC), and ultrastructural studies at one month postpartum. Twenty-four female Sprague-Dawley (SD) rats were assigned to four groups (n = 6), comprising two treatment groups administered with N?-Nitro-L-Arginine Methyl Ester Hydrochloride (L-NAME) and two control groups. All rats were sacrificed on Day 30 postpartum. The mesenteric arteries (resistance arteries) were harvested and preserved for histopathological and ultrastructural studies. Blood was taken for the biochemical study of nitric oxide (NO) and endothelin-1 (ET-1), and their concentrations were determined by enzyme-linked immunosorbent assay (ELISA). The endothelin-1 A receptor (ETAR) and endothelin-1 B receptor (ETBR) expression of the resistance arteries were measured by immunohistochemical studies. During the postpartum period, the mean concentrations of ET-1 and NO were not significantly altered in all groups, and there were no significant changes in the mean immunoreactivity of the ETAR and ETBR for the tunica intima and media. For quantitative studies, the mean media-to-lumen ratio, and the endothelial cell counts per length ratio were preserved between the control and treatment groups. Although the mean nucleus-to-cytoplasmic ratio or internal elastic lamina (IEL) thickness remained unaltered between the control and treatment groups, the ultrastructural examination using a transmission electron microscope revealed remarkable ultrastructural changes in the resistance arteries that were not visible by histopathological study. The endothelial cells of the pregnant + L-NAME (PL) group exhibit irregular nuclei, discontinuous cytoplasmic boundaries, numerous abnormal vacuolization, dilatation of subendothelial space (SES), fragmented IEL, and abundant extracellular matrix (ECM) substances below IEL. In conclusion, the endothelium of the resistance arteries of hypertension-induced pregnant rats showed substantial evidence of ultrastructural changes after postpartum. Despite there being no further insult, it indicates that there is an initial pathology for ED due to high blood pressure during HDPs. This may result in the later development of CVDs in women.