Vascular structure and oxidative stress in salt-loaded spontaneously hypertensive rats: Effects of losartan and atenolol

Abstract

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 (SHRS), 1.5% NaCl and 30mg losartan/kg/day (SHRSL), or 50mg atenolol/kg/day (SHRSA). 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 SHRS, 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. © 2010 American Journal of Hypertension, Ltd.