CARDIOPROTECTIVE ROLE OF AMLODIPINE UNDER ACUTE HYPOBARIC HYPOXIA: ROLE OF AKT-1 IN REDOX BALANCE

Hypobaric hypoxia induced systolic heart dysfunction and arrhythmia is prevalent in ascendants. L-type calcium channel blocker amlodipine plays important role in modulating cardiac function. We tested if amlodipine could impart cardio protection and restore oxidative balance under hypobaric hypoxia, by modulating HIF-1α activity and calcium accumulation, thus, protects from cardio-toxicity. Experimental animals, male Sprague-Dawley rats (180-200 g), were randomized into four groups, i.e. normoxia control (N), normoxia + amlodipine (N+AML), hypoxia control (H) and hypoxia + amlodipine (H+AML) (n=8), and exposed to hypobaric hypoxia for three time points i.e. 24 h, 48 h and 72 h to assess cellular damages. Amlodipine treatment not only restored systolic blood pressure and heart rate to normal levels under hypobaric hypoxia, but also regulated HIF-1α expression, Akt/p-Akt levels and intracellular Ca²⁺ levels ([Ca²⁺]_i).Biochemical markers of oxidative damage, i.e. glutathione reduced (GSH), glutathione oxidized (GSSG), lipid peroxidation (MDA) and free radical generation by reactive oxygen species (ROS) estimation were significantly restored by intraperitonial administration (10 mg / kg b.w.) of amlodipine. Amlodipine was found effective in regulating systolic heart function and restoring plasma MDA levels, thus help protect from hypobaric hypoxia induced damages.