Abstract 015: Maternal High Blood Pressure Control Persistently Alters Gut-Brain Communication and Attenuates Hypertension of Offspring

Abstract

Objective: Evidence suggests involvement of a dysfunctional gut-brain axis in hypertension. Maternal-fetal cross-talk is implicated in the long-term control of hypertension of offspring. Therefore, we tested the hypothesis that maternal factors influence gut-brain axis impacting hypertension in offspring. Methods: Pregnant female spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats, were treated with captopril (CAP) water (100 mg/kg/day) or sterile water throughout pregnancy and lactation. At weaning, the pups from dams drinking sterile water were continued until age 12 weeks. The pups from dams drinking CAP water were divided into two groups: offspring continuously drinking CAP and offspring withdrawn from CAP, then drinking sterile water until age 12 weeks (N=8-11/group). Results: Compared with SHR, maternal exposure of SHR to CAP lowered systolic BP in offspring at weaning (Δ=24mmHg, P<0.05). This was associated with amelioration of gut inflammation (decreased Cd3 by 2.8-fold, P<0.01) and permeability (increased Tjp1 by 4.3-fold, P<0.01; Ocln increased by 2.8-fold, P<0.01). At 12 week-old, SHR offspring exposed to maternal CAP demonstrated persistent decreased systolic BP (Δ=25mmHg, P<0.01), increased microbial Shannon diversity (Δ=1.25, P<0.001), altered β diversity, and growth of beneficial bacterial genera, compared with SHR (increased Coprococcus by 41-fold, P<0.001; Oscillospira by 4.9-fold, P<0.01; Roseburia by 83-fold, P<0.001; Mucispirillum by 26-fold, P<0.01). Decreases in activated microglia numbers per area (Δ=2.8, P<0.05) and neuroinflammation (decreased Tnf by 2.4-fold, P<0.001; Il1b by 2.7-fold, P<0.05) and improvement of gut inflammation ( Cd3 decreased by 1.8-fold, P<0.01) and permeability (increased Tjp1 by 2.2-fold, P<0.1; Ocln by 1.8-fold, P<0.1) were also observed in these SHR offspring with maternal CAP, compared with SHR. These improvements were also found in the SHR with continuous CAP. Conclusion: Maternal decrease of BP by CAP improves dysregulated gut-brain axis in SHR offspring and long-term lowering of BP. Thus, it provides conceptual support that targeting of the gut-brain axis via the mother may be a relevant strategy for the control of hypertension in the offspring.