Hesperidin inhibits L‐NAME‐induced vascular and renal alterations in rats by suppressing the renin–angiotensin system, transforming growth factor‐β1, and oxidative stress

Introduction: Neurohumoral mechanisms play an important role in the pathophysiology of congestive heart failure (HF). Recent studies suggest that the brain renin angiotensin system (RAS) plays an important role in regulating body fluids and sympathetic drive in HF. In addition, it has been shown that there is cross talk between cytokines and RAS in cardiovascular disease. In this study we determined whether blockade of brain RAS attenuate inflammatory cytokines and oxidative stress in HF rats. Methods and Results: Adult male Sprague-Dawley rats were implanted with intracerebroventricular (ICV) cannulae and subjected to coronary artery ligation to induce HF and confirmed by echocardiography. Rats were treated with an angiotensin type 1 receptors (AT1-R) antagonist losartan (LOS, 20 μg/hr, ICV) or vehicle (VEH) for 4 weeks. At the end of the study, left ventricular (LV) function was measured by echocardiography and rats were sacrificed, and brain and plasma samples were collected for measurements of cytokines and superoxide using immunohistochemistry, Western blot and real time RT-PCR. HF rats induced significant increases in Nuclear Factor-kappaB (NF-κB) p50-positive neurons and activated microglia in the paraventricular nucleus (PVN) of hypothalamus, and TNF-α, IL-1β, IL-6 and NF-κB p50 in hypothalamus when compared with sham rats. These animals also had increased staining for dihydroethidium (DHE) and plasma levels of norepinephrine (NE), an indirect indicator of sympathetic activity. In contrast, ICV treatment with LOS attenuated cytokine expression and oxidative stress in the PVN and hypothalamus when compared with VEH treated HF rats. ICV treatment with LOS also reduced plasma NE levels, and proinflammatory cytokine, heart weight to body weight ratio with decreased LV end-diastolic pressure. Conclusions : These findings suggest the cross talk between the cytokines and renin angiotensin system within the brain contribute to sympatho-excitation in HF.

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INHIBITION OF THE RENIN?ANGIOTENSIN SYSTEM ATTENUATES THE DEVELOPMENT OF LIVER FIBROSIS AND OXIDATIVE STRESS IN RATS

Clinical and Experimental Pharmacology and Physiology ◽

10.1111/j.1440-1681.2007.04797.x ◽

2007 ◽

Vol 0 (0) ◽

pp. 070928213402001-??? ◽

Cited By ~ 1

Author(s):

Ebtehal El-Demerdash ◽

Omar M Abdel Salam ◽

Seham A El-Batran ◽

Heba MI Abdallah ◽

Nermeen M Shaffie

Keyword(s):

Oxidative Stress ◽

Liver Fibrosis ◽

Renin Angiotensin System ◽

Angiotensin System ◽

Renin Angiotensin ◽

And Oxidative Stress

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Role of Renin-Angiotensin System and Oxidative Stress on Vascular Inflammation in Insulin Resistence Model

International Journal of Hypertension ◽

10.1155/2013/420979 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 15

Author(s):

N. F. Renna ◽

C. Lembo ◽

E. Diez ◽

R. M. Miatello

Keyword(s):

Oxidative Stress ◽

Experimental Model ◽

Chronic Treatment ◽

Vascular Tissue ◽

Vascular Inflammation ◽

Renin Angiotensin System ◽

Angiotensin System ◽

Renin Angiotensin ◽

The Creation ◽

And Oxidative Stress

(1) This study aims to demonstrate the causal involvement of renin angiotensin system (RAS) and oxidative stress (OS) on vascular inflammation in an experimental model of metabolic syndrome (MS) achieved by fructose administration to spontaneously hypertensive rats (FFHR) during 12 weeks. (2) Chronic treatment with candesartan (C) (10 mg/kg per day for the last 6 weeks) or 4OH-Tempol (T) (10−3 mmol/L in drinking water for the last 6 weeks) reversed the increment in metabolic variables and systolic blood pressure. In addition, chronic C treatment reverted cardiovascular remodeling but not T. (3) Furthermore, chronic treatment with C was able to completely reverse the expression of NF-κB and VCAM-1, but T only reduced the expression. C reduced the expression of proatherogenic cytokines as CINC2, CINC3, VEGF, Leptin, TNF-alpha, and MCP-1 and also significantly reduced MIP-3, beta-NGF, and INF-gamma in vascular tissue in this experimental model. T was not able to substantially modify the expression of these cytokines. (4) The data suggest the involvement of RAS in the expression of inflammatory proteins at different vascular levels, allowing the creation of a microenvironment suitable for the creation, perpetuation, growth, and destabilization of vascular injury.

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