Brain ACE2 overexpression reduces DOCA‐salt hypertension independently of endoplasmic reticulum stress (875.3)

Abstract

Endoplasmic reticulum (ER) stress was recently reported to contribute to hypertension. We previously observed that ACE2 in the paraventricular nucleus (PVN) is pivotal for blunting DOCA‐salt hypertension. To assess the contribution of ER stress, the PVN was collected from non‐transgenic (NT, n=4) and transgenic mice overexpressing brain ACE2 (SA, n=4), submitted to sham or 3 wk DOCA‐salt. ER stress (Bip, ATF4) and autophagy (LC3, LAMP2) markers were measured by Western blot. Baseline expression of Bip (1±0.07 vs. 0.96±0.11), ATF4 (1±0.06 vs. 0.99±0.02), LC3 II/I (1±0.02 vs. 1.16±0.11) and LAMP2 (1±0.08 vs. 0.97±0.05) were similar in NT and SA mice. Surprisingly, DOCA‐salt treatment did not alter these markers in NT (1.13±0.13; 1.14±0.05; 1.14±0.09; 1.13±0.09, respectively) or SA (1.04±0.04; 1.19±0.09; 1.1±0.07; 1.18±0.06, respectively) mice, despite a significant increase in blood pressure (BP, telemetry) in NT and a smaller rise in SA mice. To further assess the role of ER stress in DOCA‐salt hypertension, NT mice (n=8) were infused icv with TUDCA (5 µg/day, 21 days), an ER stress inhibitor, during DOCA‐salt treatment. DOCA‐salt alone significantly increased BP (127±5 vs. 101±2 mmHg, P<0.05), however, this increase was not affected by TUDCA (123±4 mmHg). Our data suggest that ER stress does not contribute to DOCA‐salt hypertension and that ACE2 blunts this neurogenic hypertension independently of ER stress.Grant Funding Source: Supported by AHA (12EIA830004)