Losartan reduces oxidative stress within the rostral ventrolateral medulla of rats with renovascular hypertension.

Abstract

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.

• Authors: Erika E Nishi, Cássia T Bergamaschi, Elizabeth B Oliveira-Sales, Karin A Simon, Ruy R Campos
• Journal: American journal of hypertension (Am J Hypertens) Vol. 26 Issue 7 Pg. 858-65 (Jul 2013) ISSN: 1941-7225 [Electronic] United States
• PMID: 23485486 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Thiobarbituric Acid Reactive Substances
• Superoxide Dismutase
• Losartan

Topics

• Angiotensin II Type 1 Receptor Blockers
• Animals
• Arterial Pressure (drug effects)
• Baroreflex (physiology)
• Disease Models, Animal
• Hypertension, Renovascular (drug therapy, metabolism, physiopathology)
• Losartan (therapeutic use)
• Male
• Oxidative Stress (drug effects)
• Rats
• Rats, Wistar
• Superoxide Dismutase (biosynthesis, drug effects)
• Thiobarbituric Acid Reactive Substances (metabolism)
• Treatment Outcome
• Ventral Thalamic Nuclei (drug effects, enzymology)