STRAIN-DEPENDENT RESPONSES TO BRAIN OXIDATIVE STRESS AND ARTERIAL BLOOD PRESSURE IN NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS. EFFECTS OF LOSARTAN

Experimental data suggest that oxidative stress is involved in hypertension. The aim of this study was to evaluate and compare the effect of chronic systematic treatment with AT1 receptor antagonist losartan on arterial blood pressure and the production of oxidative damage in the brain of normotensive Wistar and spontaneously hypertensive rats (SHRs). Drug administration was conducted via subcutaneous osmotic minipumps for 14 days (10 mg/kg per day). Spontaneously hypertensive rats showed an increase in the arterial blood pressure compared to normotensive Wistar rats. Long-term losartan exposure attenuated hypertension in SHRs. The level of lipid peroxidation was higher in both the frontal cortex and the hippocampus of SHRs compared to Wistar rats. However, chronic block of AT1 receptors decreased the level of lipid peroxidation of the above mentioned brain structures in Wistar and SHRs. Losartan influenced positively the citosolic superoxide dismutase (SOD/CuZn) activity in both the frontal cortex and the hippocampus of SHRs while it enhanced the activity of this antioxidant enzyme only in the hyppocampus of Wistar rats. No changes in the mitochondrial SOD/Mn activity in both the frontal cortex and the hippocampus were detected after losartan treatment in Wistar and SHRs. These data suggest that the strain differences of the level of oxidative stress in the frontal cortex and the hippocampus as well as arterial blood pressure determine different responses after long-term infusion with AT1 receptor antagonist.