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Maternal Separation-induced Increases in Vascular Stiffness are Independent of Circulating Angiotensinogen Levels.

Timothy Mahanes,M. Murphy,A. Ouyang,Frederique Yiannikouris,Bradley S. Fleenor,A. Loria

Published 2020 in Journal of applied physiology

ABSTRACT

The renin angiotensin system (RAS) precursor, angiotensinogen (AGT), has been implicated in the functional and mechanical alterations of the vascular wall in response to high fat diet (HFD). Previously, we have shown that HFD exacerbates angiotensin II-induced constriction in isolated aortic rings from male rats exposed to Maternal Separation (MatSep), a model of early life stress. The aim of this study was to investigate whether MatSep increases AGT secretion promoting vascular stiffness in rats fed a HFD. Wistar Kyoto male MatSep offspring were separated (3 hours/day, postnatal days 2-14) and undisturbed littermates were used as controls. At weaning, rats were fed 17 weeks a normal diet (ND) or HFD, 18 or 60% kcal-from-fat, respectively. In plasma, there was a main effect of MatSep reducing AGT concentration (p<0.05), but no effect due to diet. In urine, ND-fed MatSep rats displayed higher AGT concentrations that were further increased by HFD (p<0.05 vs. control). AGT mRNA abundance and protein expression were increased in adipose tissue from HFD-fed MatSep rats compared with controls (p<0.05). No significant differences in liver and kidney AGT levels were found between groups. In addition, MatSep augmented vascular stiffness assessed on freshly-isolated aortic rings from ND-fed rats (p<0.05). Yet, HFD did not worsen vascular stiffness in MatSep and control rats. There was no correlation between plasma AGT and vascular stiffness in ND-fed rats; however, this relationship was negative in HFD-fed MatSep rats (p<0.05). Therefore, this study shows that MatSep-induced increases in vascular stiffness are independent of diet or plasma AGT.

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