Collectively, our results suggest that chronic RAAS activation in (mREN2)27 HTN promotes (1) enhanced cardiac contractility through AngII-mediated AT1R stimulation and a compromised protective arm of AngII involving MAS1 and AT2 receptors and (2) disrupted calcium homeostasis due to increased NCX activity and decreased SERCA2 activity. The gene discussed is MAS1; the disease is hypertensive disorder.