Losartan Reduces Oxidative Stress Within the Rostral Ventrolateral Medulla of Rats With Renovascular Hypertension

Previous studies showed that the microinjection of antioxidants or the overexpression of superoxide dismutase within the rostral ventrolateral medulla (RVLM) reduces hypertension and sympathoexcitation in the 2-kidney, 1-clip (2K-1C) model. In this study, we hypothesized that angiotensin II (ANG II) type 1 receptor (AT(1)R) is involved in the oxidative stress within the RVLM and contributes to cardiovascular dysfunction in renovascular hypertension. Losartan (30mg/kg/day, oral gavage) was administered for 7 consecutive days by week 5 after implantation of the clip (gap width 0.2mm). Mean arterial pressure, baroreflex, and renal sympathetic nerve activity (rSNA) were evaluated. Superoxide production was evaluated by dihydroethidium (DHE) staining within the RVLM and within a control area. Systemic oxidative stress was characterized by measurement of thiobarbituric acid reactive substances (TBARS) and total glutathione (tGSH) in the blood. AT(1)R blockade significantly (P < 0.05) reduced hypertension by approximately 20% (n 11) and sympathoexcitation to the kidneys by approximately 41% (n 6) in the 2K-1C rats. Losartan treatment increased the baroreflex sensitivity of rSNA to pressor (67%) and depressor (140%) stimuli in the 2K-1C rats. AT(1)R blockade caused a significant (66%) reduction in DHE staining within the RVLM but not within the control area, reduced plasma TBARS (from 1.60.1 to 1.00.1 nmol/ml), and increased tGSH (from 3.40.4 to 5.20.3 mol/g Hb) in the 2K-1C group only. Our findings suggest that the beneficial effects of ANG II blockade in renovascular hypertension are partly due to preferential reduction of oxidative stress in the RVLM.