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

• Published in: American journal of hypertension 2013-07, Vol.26 (7), p.858-865
• Main Authors: Nishi, Erika E., Bergamaschi, Cássia T., Oliveira-Sales, Elizabeth B., Simon, Karin A., Campos, Ruy R.
• Format: Article
• Language: English
• Subjects: Angiotensin II Type 1 Receptor Blockers; Animals; Arterial Pressure - drug effects; Baroreflex - physiology; Disease Models, Animal; Hypertension; Hypertension, Renovascular - drug therapy; Hypertension, Renovascular - metabolism; Hypertension, Renovascular - physiopathology; Losartan - therapeutic use; Male; Oxidative stress; Oxidative Stress - drug effects; Rats; Rats, Wistar; Reflexes; Rodents; Superoxide Dismutase - biosynthesis; Superoxide Dismutase - drug effects; Thiobarbituric Acid Reactive Substances - metabolism; Treatment Outcome; Ventral Thalamic Nuclei - drug effects; Ventral Thalamic Nuclei - enzymology
• ISSN: 0895-7061; 1941-7225
• DOI: 10.1093/ajh/hpt037

Background 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 (AT1R) is involved in the oxidative stress within the RVLM and contributes to cardiovascular dysfunction in renovascular hypertension. Methods 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. Results AT1R 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. AT1R blockade caused a significant (66%) reduction in DHE staining within the RVLM but not within the control area, reduced plasma TBARS (from 1.6±0.1 to 1.0±0.1 nmol/ml), and increased tGSH (from 3.4±0.4 to 5.2±0.3 μmol/g Hb) in the 2K-1C group only. Conclusions 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.