Increased uterine arterial tone, stiffness and remodeling with augmented matrix metalloproteinase-1 and -7 in uteroplacental ischemia-induced hypertensive pregnancy

Apr 21, 2024Biochemical pharmacology

Higher uterine artery tightness, stiffness, and changes linked to increased tissue-breaking enzymes in pregnancy with poor placenta blood flow and high blood pressure

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Blood pressure was higher and litter size and pup weight were reduced in rats with reduced uteroplacental perfusion pressure (RUPP) compared to normal pregnant (Preg) rats.

Increased uterine arterial active myogenic, passive, and endothelium-dependent tone was observed in RUPP compared to Preg rats.
Greater total vascular tone in RUPP was indicated by smaller diameter changes in response to increased intraluminal pressure.
Uterine arteries in RUPP exhibited leftward shifts in total and passive strain-stress curves, suggesting increased arterial stiffness.
Histological analysis showed decreased lumen/total and increased wall/total area in RUPP arteries.
Elevated levels of matrix metalloproteinases (MMP-1 and MMP-7) in RUPP indicated uterine arterial remodeling.

AI simplified

Preeclampsia is a pregnancy-related disorder manifested as hypertensive pregnancy (HTN-Preg) and often fetal growth restriction (FGR), but the mechanisms involved are unclear. We have reported enhanced reactivity of systemic vessels in HTN-Preg rats, but the critical changes in the uterine circulation are less clear. We tested whether HTN-Preg involves localized aberrations in uterine arterial tone, stiffness and remodeling by matrix metalloproteinases (MMPs). Blood pressure (BP) and litter size were recorded in normal pregnant (Preg) rats and Preg rats with reduced uteroplacental perfusion pressure (RUPP). Isolated uterine arteries were placed in a pressure myograph for measuring intrinsic and extrinsic tone and arterial stiffness. Arteries were bathed in normal Krebs solution (2.5 mM Ca), Ca-free (2 mM EGTA) Krebs, treated with sodium nitroprusside (SNP), or endothelium denuded, then pressurized at 10 mmHg steps from 10 to 110 mmHg, and the % change in diameter was analyzed to measure total (active + passive), active Ca-dependent myogenic, passive, and endothelium-dependent tone, respectively. BP was higher and the litter size and pup weight were reduced in RUPP vs Preg rats. In normal Krebs, increasing intraluminal pressure caused smaller increments in diameter in arteries of RUPP vs Preg rats, suggesting greater total vascular tone. Arterial incubation in Ca-free Krebs, treatment with SNP or endothelium-removal abolished the differences in vascular tone, and subtraction of each of these components from total vascular tone revealed significant active Ca-dependent myogenic, passive, and endothelium-dependent tone, respectively, in RUPP vs Preg rats. The total and passive strain-stress curves were shifted leftward in arteries of RUPP vs Preg rats, indicating increased uterine arterial stiffness. Arterial sections showed decreased lumen/total and increased wall/total area, and immunohistochemistry revealed greater MMP-1 and MMP-7 staining particularly in the media, suggesting uterine arterial remodeling by MMPs in RUPP vs Preg rats. The increased uterine arterial active myogenic, passive, and endothelium-dependent tone, arterial stiffness and remodeling by MMPs would further reduce uterine blood flow and exacerbate uteroplacental ischemia, FGR and HTN-Preg. 2+ 2+ 2+ 2+ 2+

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

Increased uterine arterial tone, stiffness and remodeling with augmented matrix metalloproteinase-1 and -7 in uteroplacental ischemia-induced hypertensive pregnancy

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief