Thus, the aim of this study was to show in a rat experimental model of spontaneous hypertension (spontaneously hypertensive rats, SHRs) whether ARNI or ivabradine are able to protect a hypertensive heart and whether this potential protection is due to their interaction with the deleterious classical ACE/Ang II/AT1R pathway and the protective alternative ACE2/Ang 1-7/Mas receptor (MasR) pathway of the renin–angiotensin system. The gene discussed is REN; the disease is hypertensive disorder.