Human myometrial artery function and endothelial cell calcium signalling are reduced by obesity: can this contribute to poor labour outcomes?

Prendergast, Clodagh ORCID: 0000-0002-7678-7693 and Wray, Susan ORCID: 0000-0002-0086-1359 (2019) Human myometrial artery function and endothelial cell calcium signalling are reduced by obesity: can this contribute to poor labour outcomes? Acta physiologica (Oxford, England), 227 (4). e13341-e13341.

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Official URL: http://dx.doi.org/10.1111/apha.13341

Abstract

AIMS:Determining how obesity affects function in human myometrial arteries, to help understand why childbirth has poor outcomes in obese women. METHODS:Myometrial arteries were studied from 84 biopsies. Contraction (vasopressin and U-46619) and relaxation (carbachol, bradykinin, SNAP) was assessed using wire myography. eNOS activity was assessed using L-NAME. Cholesterol was reduced using methyl-β-cyclodextrin to determine whether it altered responses. Differences in endothelial cell intracellular Ca2+ signalling were assessed using confocal microscopy. RESULTS:The effects of BMI on relaxation were agonist specific and very marked; all vessels, irrespective of BMI, relaxed to bradykinin but 0% of vessels (0/13) from obese women relaxed to carbachol, compared to 59% (10/17) from normal weight women. Cholesterol-lowering drugs did not restore carbachol responses (n=6). All vessels, irrespective of BMI, relaxed when NO was directly released by SNAP (n=19). Inhibition of eNOS with L-NAME had a significant effect in normal but not overweight/obese vessels. Compared to bradykinin, a lower proportion of endothelial cells responded to carbachol and the amplitude of the calcium response was significantly less, in all vessels. Furthermore, a significantly lower proportion of endothelial cells responded to carbachol in the overweight/obese group compared to control. In contrast to relaxation, the effect of contractile agonists was unchanged with increasing BMI. CONCLUSIONS:The ability of human myometrial arteries to relax is significantly impaired with obesity, and our data suggest this is due to a deficit in endothelial calcium signalling. This inability to recover following compression during contractions, might contribute to poor labours in obese women. This article is protected by copyright. All rights reserved.

Item Type:	Article
Uncontrolled Keywords:	BMI, Ca2+ signalling, endothelium, myometrial arteries, obesity
Depositing User:	Symplectic Admin
Date Deposited:	18 Jul 2019 09:07
Last Modified:	19 Jan 2023 00:37
DOI:	10.1111/apha.13341
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3050068