Angiotensin‐II receptors regulate ACE2 expression in the brain

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We previously reported the presence of ACE2 in brain nuclei involved in the central regulation of blood pressure (BP). Using real-time PCR, we tested the hypothesis that angiotensin-II receptors blockade would modulate ACE2 expression in these brain regions. Non-transgenic (NT) and transgenic mice (n=6 per group) with brain-selective overexpression of AT1a receptors (NSE-AT1) were instrumented with radiotelemeters for continuous BP monitoring. Baseline BP (mmHg) was recorded for 1 wk before subcutaneous implantation of osmotic pumps containing saline, an AT1 blocker (losartan, 10 mg/Kg/day) or an AT2 antagonist (PD123319, 10 mg/Kg/day). Mice were infused and BP recorded for 2 wks. In losartan-treated mice, mean BP decreased significantly (NT:−10±3; NSE-AT1:−12±3; P<0.05) by 2 wks but remained unchanged in the saline groups (NT:−1±2; NSE-AT1:-2±3). On the other hand, AT2 blockade increased BP only in NSE-AT1 (12±5; P<0.05) mice. Basal ACE2 mRNA expression was increased in the nucleus of tractus solitarius (NT:1±0.1; NSE-AT1:1.3±0.2; P<0.05) and decreased in the ventrolateral medulla (NT:1±0.1; NSE-AT1:0.7±0.1; P<0.05) of NSE-AT1 mice but was similarly decreased by losartan (NT:0.5±0.1; NSE-AT1:0.7±0.1 and NT:0.6±0.1; NSE-AT1:0.4±0.1, respectively, P<0.05) in both genotypes. On the contrary, AT2 blockade increased ACE2 expression in these regions (NT:1.9±0.4; NSE-AT1:1.5±0.2 and NT:1.9±0.3, respectively, P<0.05). These data suggest that both AT1 and AT2 receptors regulate ACE2 expression in brain regions controlling BP, confirming the involvement of brain ACE2 in the central regulation of cardiovascular function. (NS52479)