Vascular structure and oxidative stress in salt-loaded spontaneously hypertensive rats: effects of losartan and atenolol
| Autor: | Jorge E. Toblli, León Ferder, Elena M.V. de Cavanagh, Inés Stella, Marcelo Ferder, Felipe Inserra |
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| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Nitric Oxide Synthase Type III medicine.disease_cause Rats Inbred WKY Losartan Renin-Angiotensin System chemistry.chemical_compound Renal Artery Superoxides Internal medicine medicine.artery Malondialdehyde Rats Inbred SHR Internal Medicine medicine Animals Sodium Chloride Dietary Aorta Angiotensin II receptor type 1 biology business.industry Atenolol Angiotensin II Rats Nitric oxide synthase Oxidative Stress Endocrinology chemistry Hypertension cardiovascular system biology.protein business Angiotensin II Type 1 Receptor Blockers Oxidative stress circulatory and respiratory physiology medicine.drug |
| Zdroj: | American journal of hypertension. 23(12) |
| ISSN: | 1941-7225 |
| Popis: | Background Renin-angiotensin system (RAS) modulation by high dietary sodium may contribute to salt-induced hypertension, oxidative stress, and target organ damage. We investigated whether angiotensin II (Ang-II) type 1 (AT1)-receptor blockade (losartan) could protect the aorta and renal arteries from combined hypertension- and high dietary salt-related oxidative stress. Methods Spontaneously hypertensive rats (3-month-old, n = 10/group) received tap water (SHR), water containing 1.5% NaCl (SHR+S), 1.5% NaCl and 30 mg losartan/kg/day (SHR+S+L), or 50 mg atenolol/kg/day (SHR+S+A). Atenolol was used for comparison. Ten Wistar-Kyoto rats (WKY) were controls. Systolic blood pressure (SBP) was determined by tail plethysmography. After 5 months of treatment, vascular remodeling and oxidative stress (superoxide production and NAD(P)H-oxidase activity (chemiluminescence), malondialdehyde (MDA) content (high-performance liquid chromatography), endothelial nitric oxide synthase (eNOS) activity [(14)C-arginine to (14)C citrulline], CuZn-SOD activity (spectrophotometry)) were studied. Results In SHR, salt-loading significantly aggravated hypertension, urinary protein excretion, intraparenchymal renal artery (IPRArt) perivascular fibrosis, aortic and renal artery oxidative stress, and induced endothelial cell loss in IPRArts. In salt-loaded SHR, 5-month losartan and atenolol treatments similarly reduced SBP, but only losartan significantly prevented (i) urinary protein excretion increase, (ii) or attenuated hypertension-related vascular remodeling, (iii) aortic MDA accumulation, (iv) renal artery eNOS activity lowering, and (v) aortic and renal artery superoxide dismutase (SOD) activity reduction. In SHR+S, the contributions to aortic superoxide production were as follows: uncoupled eNOS > xanthine oxidase (XO) > NAD(P)H oxidase. Conclusions In this salt-sensitive genetic hypertension model, losartan protects from hypertension- and high dietary salt-related vascular oxidative stress, exceeding the benefits of BP reduction. Also, during salt overload, BP-independent factors contribute to vascular remodeling, at least part of which derive from AT1-receptor activation. |
| Databáze: | OpenAIRE |
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