Enhanced angiotensin II‐induced aortic constriction in maternally separated rats is endothelium‐dependent and reactive oxygen species (ROS)‐independent.

Abstract

We previously have reported that Angiotensin II (AngII)‐induced constriction is enhanced in rats subjected to Maternal Separation (MS), a model of early life stress. The aim of this study was to investigate whether NO and/or ROS are involved in the increased Ang II‐induced constriction in MS rats. Male Wistar Kyoto rats were separated from their mother 3 hs/day from day 2 to 14 of life. Unseparated rats (MU) were used as control. Dose‐response curves to AngII (10−12 to 10−4.5 mol/L) were performed in endothelium‐intact and denuded thoracic aortic rings from MS and MU adult rats. NO basal tone was determined using a single dose of PE (10−8M, ±L‐NAME 100 μM). Inhibition of NOS in endothelium‐intact rings increased the % maximal vasoconstriction (% max VC) in MU rats (3.0±0.2 fold). After NOS inhibition, increase in % max VC was attenuated in MS rats (1.5±0.2 fold, p<0.05 vs. MU). Denuded rings showed similar % max VC in both groups. NO basal tone was reduced in MS rats (44.9±7.4 vs. 20.0±4.0, p<0.05). Inhibition of ROS with PEG‐SOD (1000 mU/L) or apocynin (300 μM) decreased the % max VC in MU rats (27.8±3.4 vs. 7.2±0.8 and 9.1±1.9, respectively, p<0.05). Either PEG‐SOD or apocynin did not modify the % max VC in MS rats. These data indicate that MS induces a dysfunction in Ang II mediated signaling in the endothelium, suggesting that early life stress mediates a pro‐contractile vascular phenotype.