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Inhibition of iNOS protects endothelial-dependent vasodilation in aged rats.

Tian J, Yan Z, Wu Y, Zhang SL, Wang K, Ma XR, Guo L, Wang J, Zuo L, Liu JY, Quan L, Liu HR - Acta Pharmacol. Sin. (2010)

Bottom Line: Vasorelaxation was measured in isolated thoracic aorta. iNOS expression of thoracic aortic arteries was detected using immunohistochemistry and Western blot.However, the maximal relaxation induced by acidified NaNO2 (an endothelium-independent vasodilator) had no significant difference between the two groups.The mechanism was related with attenuation of peroxynitrite formation.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Shanxi Medical University, Taiyuan, China.

ABSTRACT

Aim: To examine whether iNOS contributes to endothelial dysfunction in aged rats.

Methods: Male Sprague Dawley rats were divided into three groups: young rats, aged rats treated with vehicle and aged rats treated with N-[3-(Aminomethyl) benzyl] acetamidine (1400W, 1 mg/kg, ip). Vasorelaxation was measured in isolated thoracic aorta. iNOS expression of thoracic aortic arteries was detected using immunohistochemistry and Western blot. Nitrotyrosine (a marker for peroxynitrite formation) content and expression in thoracic aortic tissue were determined using enzyme linked immunosorbent assay and immunohistochemistry.

Results: Maximal relaxation induced by acetylcholine (10⁻⁹ to 10⁻⁵ mol/L) in the aged rats treated with vehicle was significantly decreased (70%±15%, P<0.01), as compared with the young rats (95%±8%). However, the maximal relaxation induced by acidified NaNO2 (an endothelium-independent vasodilator) had no significant difference between the two groups. Moreover, iNOS and nitrotyrosine expression increased in the vessels of the aged rats. In the aged rats treated with 1400W (a highly selective iNOS inhibitor) nitrotyrosine expression was reduced and acetylcholine-induced vasorelaxation was markedly improved (maximal relaxation was increased to 87%±8%, P<0.05), but the acidified NaNO₂-induced vasorelaxation had no significant change.

Conclusion: Our study demonstrated that inhibition of iNOS by 1400W increased endothelium-dependent vasodilation in aged rats. The mechanism was related with attenuation of peroxynitrite formation.

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Effect of 1400W, a selective iNOS inhibitor, on nitrotyrosine (NT) staining (A, DAB staining, ×40) and vascular nitrotyrosine content (B) in aged rats. cP<0.01 vs young group; eP<0.05 vs aging group. n=7 rats per group.
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fig3: Effect of 1400W, a selective iNOS inhibitor, on nitrotyrosine (NT) staining (A, DAB staining, ×40) and vascular nitrotyrosine content (B) in aged rats. cP<0.01 vs young group; eP<0.05 vs aging group. n=7 rats per group.

Mentions: To determine the possible mechanisms of 1400W vasculoprotection, we investigated the content and expression of nitrotyrosine in aortic vessels of aged rats. As illustrated in Figure 3A, strong nitrotyrosine staining was detected in endothelial cells and smooth muscle cells from aged rats, and treatment with 1400W reduced nitrotyrosine staining. Quantitative ELISA results indicated that a 5.7-fold increase in nitrotyrosine content was observed in aged tissue, and this increased nitrotyrosine content was markedly reduced by in vivo administration of 1400W (Figure 3B).


Inhibition of iNOS protects endothelial-dependent vasodilation in aged rats.

Tian J, Yan Z, Wu Y, Zhang SL, Wang K, Ma XR, Guo L, Wang J, Zuo L, Liu JY, Quan L, Liu HR - Acta Pharmacol. Sin. (2010)

Effect of 1400W, a selective iNOS inhibitor, on nitrotyrosine (NT) staining (A, DAB staining, ×40) and vascular nitrotyrosine content (B) in aged rats. cP<0.01 vs young group; eP<0.05 vs aging group. n=7 rats per group.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4012905&req=5

fig3: Effect of 1400W, a selective iNOS inhibitor, on nitrotyrosine (NT) staining (A, DAB staining, ×40) and vascular nitrotyrosine content (B) in aged rats. cP<0.01 vs young group; eP<0.05 vs aging group. n=7 rats per group.
Mentions: To determine the possible mechanisms of 1400W vasculoprotection, we investigated the content and expression of nitrotyrosine in aortic vessels of aged rats. As illustrated in Figure 3A, strong nitrotyrosine staining was detected in endothelial cells and smooth muscle cells from aged rats, and treatment with 1400W reduced nitrotyrosine staining. Quantitative ELISA results indicated that a 5.7-fold increase in nitrotyrosine content was observed in aged tissue, and this increased nitrotyrosine content was markedly reduced by in vivo administration of 1400W (Figure 3B).

Bottom Line: Vasorelaxation was measured in isolated thoracic aorta. iNOS expression of thoracic aortic arteries was detected using immunohistochemistry and Western blot.However, the maximal relaxation induced by acidified NaNO2 (an endothelium-independent vasodilator) had no significant difference between the two groups.The mechanism was related with attenuation of peroxynitrite formation.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Shanxi Medical University, Taiyuan, China.

ABSTRACT

Aim: To examine whether iNOS contributes to endothelial dysfunction in aged rats.

Methods: Male Sprague Dawley rats were divided into three groups: young rats, aged rats treated with vehicle and aged rats treated with N-[3-(Aminomethyl) benzyl] acetamidine (1400W, 1 mg/kg, ip). Vasorelaxation was measured in isolated thoracic aorta. iNOS expression of thoracic aortic arteries was detected using immunohistochemistry and Western blot. Nitrotyrosine (a marker for peroxynitrite formation) content and expression in thoracic aortic tissue were determined using enzyme linked immunosorbent assay and immunohistochemistry.

Results: Maximal relaxation induced by acetylcholine (10⁻⁹ to 10⁻⁵ mol/L) in the aged rats treated with vehicle was significantly decreased (70%±15%, P<0.01), as compared with the young rats (95%±8%). However, the maximal relaxation induced by acidified NaNO2 (an endothelium-independent vasodilator) had no significant difference between the two groups. Moreover, iNOS and nitrotyrosine expression increased in the vessels of the aged rats. In the aged rats treated with 1400W (a highly selective iNOS inhibitor) nitrotyrosine expression was reduced and acetylcholine-induced vasorelaxation was markedly improved (maximal relaxation was increased to 87%±8%, P<0.05), but the acidified NaNO₂-induced vasorelaxation had no significant change.

Conclusion: Our study demonstrated that inhibition of iNOS by 1400W increased endothelium-dependent vasodilation in aged rats. The mechanism was related with attenuation of peroxynitrite formation.

Show MeSH
Related in: MedlinePlus