Irbesartan May Ameliorate Ventricular Remodeling by Inhibiting CREB-Mediated Cardiac Aldosterone Synthesis in Rats...

Irbesartan improves ventricular remodeling (VR) following myocardial infarction (MI). This study investigates whether irbesartan attenuates VR by reducing aldosterone production in the heart and its underlying mechanisms. MI was induced in male Sprague-Dawley rats through coronary artery ligation. The MI rats were randomly assigned to two groups: one received a vehicle, and the other received 100 mg/kg/day of irbesartan for 5 weeks. Cardiac function and myocardial fibrosis were assessed using echocardiography and Masson's trichrome staining, respectively. The impact of angiotensin II (Ang II) stimulation on cardiac microvascular endothelial cells (CMECs) from commercial sources was determined using ELISA, real-time PCR, and Western blotting. Irbesartan reduced left ventricular mass index, collagen composition, and aldosterone levels while enhancing cardiac function in MI rats. In vitro, Ang II time-dependently stimulated aldosterone secretion and CYP11B2 mRNA expression in CMECs (p < 0.05). Additionally, Ang II significantly upregulated p-CREB protein levels. However, these effects were abrogated by irbesartan and partially attenuated by CaMK inhibitor KN93 (p < 0.05). In conclusion, our study demonstrated that improvement in VR by irbesartan coincided with reduced CREB phosphorylation in CMECs and reduced aldosterone synthesis in the non-infarcted tissue. These effects may be mediated by blocking the AT1 receptor.