eprosartan and Inflammation

The aim: To evaluate the potential protective effect of Eprosartan (ARB) in bilateral renal IRI in male rats.. Materials and methods: 20 Sprague-Dawley rats divided into four groups. Sham group had surgery without IRI. Control group was subjected to 30 min ischemia and 2 hours of reperfusion. Vehicle group received 14 ml/kg (IP) injection of solvent mixture containing (10% DMSO, 40% PEG300, 5% Tween-80, and 45% normal saline) 30 minutes before clamping. Eprosartan-treated group with 30 mg/kg Eprosartan intraperitoneally 30 min before occlusion of renal pedicles followed by 30 minutes of ischemia and 2 hours of reperfusion. Serum BUN and Creatinine used to assess renal function. Renal tissue was used to measure the levels of TNF-α, IL-1β, IL-6, F2-isoprostane, and Caspase3 were measured by assessment of renal tissue. Histopathological examinations were conducted to detect parenchymal damage.. Results: Mean serum levels of BUN and Creatinine as well as mean renal tissue levels of TNF-α, IL-1β, IL-6, F2-isoprostane, and Caspase3 were significantly increased in control and vehicle groups together with increase in histological damage score compared to sham group, whereas treatment of rats with Eprosartan resulted in significant reduction in mean serum levels of BUN and Creatinine and mean renal tissue levels of TNF-α, IL-1β, IL-6, F2-isoprostane, and Caspase3 and obvious reduction in tissue injury.. Conclusions: This study demonstrates that Eprosartan pretreatment enhances kidney function by decreasing serum BUN and Creatinine, oxidative stress, cytokines, and apoptotic markers.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Creatinine; F2-Isoprostanes; Inflammation; Interleukin-6; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Tumor Necrosis Factor-alpha

Topics: Acrylates; Animals; Antioxidants; Becaplermin; Chemical and Drug Induced Liver Injury; Fibrosis; Glutathione; Glutathione Disulfide; Glutathione Peroxidase; Glutathione Reductase; Imidazoles; Inflammation; Liver; Male; Mangifera; Oxidative Stress; Quercetin; Rats; Rats, Wistar; Superoxide Dismutase; Thioacetamide; Thiophenes; Tumor Necrosis Factor-alpha

Angiotensin II (Ang II) is a potent vasoconstrictor and induces inflammation and end-organ injury through its activation of the proinflammatory transcription factor, nuclear factor-kappaB (NF-kappaB). Heat shock (HS) treatment with subsequent expression of heat shock proteins (Hsps) is an effective strategy for tissue protection against oxidative injuries. Recently, HS and Hsps have been shown to interact with NF-kappaB in tissue injury. In this study, we investigated whether HS could protect against Ang II-induced hypertension and inflammation by inhibiting NF-kappaB. Sprague-Dawley rats were divided into control and HS groups. Control and 24-hour post-heat shocked rats were treated with Ang II. At days 1, 3, 5, 7, 11, and 14 after Ang II administration, systolic blood pressures were measured by tail-cuff plethysmography, and aorta tissues were collected. Aorta NF-kappaB deoxyribonucleic acid-binding activity was measured by electrophoretic mobility shift assay, and NF-kappaB p65 subunit, Hsp70, Hsp27, and interleukin-6 (IL-6) expressions were measured by Western analysis. HS treatment significantly decreased Ang II-induced hypertension. The activation of NF-kappaB in aorta by Ang II was suppressed by HS treatment. The elevated expression of IL-6 induced by Ang II treatment was also decreased by HS treatment. Although Ang II treatment induced an increase in Hsp70 and Hsp27, HS treatment induced a greater elevation of Hsp70 and Hsp27 expression. HS treatment protects against Ang II-induced hypertension and inflammation. This protection may relate to the interaction of Hsps and the NF-kappaB pathway.

Topics: Acrylates; Angiotensin II; Animals; Antihypertensive Agents; Aorta; Blood Pressure; Blotting, Western; Electrophoretic Mobility Shift Assay; Heat-Shock Response; Hot Temperature; HSP70 Heat-Shock Proteins; Hydralazine; Hypertension; Imidazoles; Inflammation; Interleukin-6; Intracellular Signaling Peptides and Proteins; Male; NF-kappa B; NF-kappa B p50 Subunit; Norepinephrine; Protein Serine-Threonine Kinases; Rats; Rats, Sprague-Dawley; Thiophenes; Transcription Factor RelA

Antagonists of the renin-angiotensin system, such as angiotensin type 1 (AT(1)) receptor inhibitors and angiotensin-converting enzyme inhibitors, are becoming increasingly popular agents in treating patients with systemic hypertension and minimizing organ damage. In the present study, we compared the effects of eprosartan, an AT(1) receptor inhibitor, with the diuretic hydrochlorothiazide in a group of newly diagnosed hypertensive patients with multiple risk factors for atherosclerosis. The subjects were monitored and tested at 0 and 4 weeks to determine their individual effects on vascular and inflammatory markers. Although blood pressure reduction was comparable between the 2 agents, there were notable differences in their effects on markers of inflammation and oxidation. We observed a 28% reduction in neutrophil superoxide anion generating capacity, a 34% reduction in soluble monocyte chemotactic protein-1, and a 35% reduction in soluble vascular cell adhesion molecule with eprosartan therapy (all p <0.05 from the start of therapy). In addition, eprosartan showed further benefit in its ability to increase low-density lipoprotein oxidation lag time, suggesting an increased resistance to oxidation and/or modification of low-density lipoprotein. Although hydrochlorothiazide was effective in blood pressure reduction, there were no significant changes in any of the above parameters after 4 weeks of treatment. These findings suggest that eprosartan, an AT(1) receptor inhibitor, effectively reduces systemic blood pressure and, compared with hydrochlorothiazide, suggests additional benefits in the vasculature by inhibiting mechanisms of inflammation and oxidation.

Topics: Acrylates; Adult; Angiotensin Receptor Antagonists; Antihypertensive Agents; Blood Pressure; Chemokine CCL2; Dose-Response Relationship, Drug; Female; Gene Expression Regulation; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Inflammation; Lipoproteins, LDL; Male; Middle Aged; Muscle, Smooth, Vascular; Oxidation-Reduction; Receptors, Angiotensin; Renin-Angiotensin System; Thiophenes; Treatment Outcome; Vascular Cell Adhesion Molecule-1