Maternal separation-induced increases in vascular stiffness are independent of circulating angiotensinogen levels.

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 showed 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. Thus, the aim of this study was to investigate whether MatSep increases AGT secretion promoting vascular stiffness in rats fed a HFD. Male Wistar-Kyoto MatSep offspring were separated (3 h/day, postnatal days 2-14), and undisturbed littermates were used as controls. At weaning, rats were fed for 17 wk a normal diet (ND) or a HFD, 18% or 60% kcal from fat, respectively. In plasma, there was a main effect of MatSep reducing AGT concentration ( < 0.05) but no effect due to diet. In urine, ND-fed MatSep rats displayed higher AGT concentrations that were further increased by HFD ( < 0.05 vs. control). AGT mRNA abundance and protein expression were increased in adipose tissue from HFD-fed MatSep rats compared with control rats ( < 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 ( < 0.05), yet HFD did not worsen vascular stiffness in either MatSep or 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 only ( < 0.05). Therefore, this study shows that MatSep-induced increases in vascular stiffness are independent of diet or plasma AGT. This study demonstrates that there was no correlation between circulating levels of angiotensinogen (AGT) and the development of vascular stiffness in rats exposed to early-life stress and fed a normal diet. This study also shows that early-life stress-induced hypersensitive vascular contractility to angiotensin II in rats fed a high-fat diet is independent of circulating levels of AGT and occurs without further progression of vascular stiffness. Our data show that early-life stress primes the adipose tissue to secrete AGT in a sex- and species-independent fashion.