Early life stress‐induced exaggerated AngII aortic vasoconstriction is transmitted to the F1 generation

Abstract

Previously, we showed that maternal separation (MS), a model of early life stress, reduces creatinine clearance (Ccr) and enhances angiotensin II (AngII)‐induced aortic vasoconstriction via reduced nitric oxide (NO) buffering in male rats. We hypothesized that this phenotype would be transmitted to the first generation (F1) of male offspring from MS parents. Normally‐reared rats (12 weeks old) from either MS (MSF1) or control WKY parents were placed in metabolic cages. Food and water intake, body weight, and Ccr were all similar in control and MSF1 rats. Wire myography was performed to assess aortic vasoconstrictive responses to AngII in the presence and absence of the NO synthase inhibitor (L‐NAME, 100 μM, 15 min). Aorta from MSF1 compared to control rats showed greater sensitivity (log EC50: −8.51±0.14 vs. −7.93±0.12, p<0.05) and exaggerated vasoconstriction to AngII (9.38±0.8 vs. 4.8±0.3 % KCl, p<0.05). Exacerbated AngII‐induced constriction due the pre‐incubation with L‐NAME, was greater in aorta from control compared to MSF1 rats (delta % max constriction: 34.7±4.3 vs. 13.2±2.1, p<0.05). KCl induced aortic vasoconstriction was similar in control and MSF1 rats. These data indicate that the MSF1 rats maintains the vascular phenotype with reduced aortic NO buffering to AngII‐induced vasoconstriction, thus, suggesting a role for an epigenetic mechanism(s).