Abstract Body: Introduction: Hypertension remains a leading contributor to cardiovascular morbidity and mortality, with overactivation of the renin-angiotensin-aldosterone system (RAAS) playing a pivotal role in promoting oxidative stress, mitochondrial dysfunction, and adverse cardiac remodeling. The transgenic (mRen2)27 rat is a well-characterized model of Angiotensin II (Ang II)-dependent hypertension, marked by severe RAAS dysregulation and end-organ damage. Objective: This study aimed to assess whether chronic blockade of the angiotensin II type 1 receptor (AT₁R) with candesartan can restore systemic RAAS peptide balance and cardiac mitochondrial proteomic signatures in (mRen2)27 hypertensive rats. Methods: Male (mRen2)27 rats received daily intraperitoneal injections of candesartan (16 mg/kg) for four weeks. Systolic blood pressure was measured via tail-cuff plethysmography. Plasma levels of Ang II and Ang-(1-7) were quantified by radioimmunoassay. The left ventricular proteomic landscape was established in treated and untreated conditions using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine changes in the cardiac proteome. Results: Untreated (mRen2)27 rats exhibited significantly higher systolic blood pressure (SBP) compared to normotensive Hannover Sprague Dawley (HnSD) controls (190±4 vs. 123±3 mmHg; n=10; p<0.00001). Candesartan reduced SBP to 119±4.4 mmHg; (n=6; p<0.00001). Proteomic analysis of the left ventricle revealed normalization of several key proteins involved in oxidative stress and calcium regulation: superoxide dismutase 1 (Sod1), glutathione S-transferase Mu 2 (Gstm2), succinate dehydrogenase subunit B (Sdhb), voltage-dependent anion channel 3 (Vdac3), and calsequestrin 2 (Casq2). Conclusion: Chronic AT₁R inhibition via candesartan not only corrects systemic hemodynamics and RAAS dysregulation but also reverses maladaptive proteomic changes in the hypertensive myocardium. These findings suggest that Sod1, Gstm2, Sdhb, Vdac3, and Casq2 may serve as molecular targets for cardioprotection in RAAS-mediated hypertension. Targeting mitochondrial redox and calcium-handling pathways may offer new therapeutic avenues for treating RAAS-driven hypertension.