Role of an Angiotensin II Type-1 Receptor (AT

Mg²⁺ deficiency has been linked to oxidative stress, inflammation, and hypertension. We have previously shown that Losartan increases plasma Mg²⁺ levels in Dahl salt-sensitive (Dahl) rats, suggesting that defective Mg²⁺ metabolism in this strain contributes to hypertension. Here, we investigated the effects of dietary Mg²⁺ supplementation (0.3% MgO) and/or Losartan (10 mg/kg/day, in drinking water) in male Dahl rats fed a high-NaCl (8%) or standard Na⁺ diet for six weeks. Six-week-old rats were randomly assigned to eight experimental groups. NO metabolites (nitrites and nitrates) were measured in plasma and kidney homogenates. Oxidative stress was assessed by lipid peroxidation in plasma and red blood cell ghosts (RBCG), and by erythrocyte osmotic fragility (OS₅₀). Both Losartan and Mg²⁺ supplementation protected against hypertension and high-salt-induced systemic and local oxidative stress, with differential regulation of Na⁺/K⁺-ATPase and Na⁺-ATPase activity. A consistent "high Na⁺ effect" was observed across NaCl-fed groups, characterized by Renin-Angiotensin-Aldosterone System (RAAS) activation, increased Reactive Oxygen Species (ROS) production, lipid peroxidation, osmotic fragility, and elevated Na⁺/K⁺-ATPase activity. Losartan normalized blood pressure (BP) by attenuating renal RAAS activity and reducing oxidative stress, whereas Mg²⁺ supplementation increased (Nitrites + Nitrates) NO