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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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Related in: MedlinePlus

Effects of aging and 1400W treatment on vascular inducible nitric oxide synthase (iNOS) immunostaining (A, DAB staining, ×40) and iNOS expression (B, Western blot). cP<0.01 vs young group; eP<0.05 vs aging group. n=7 rats per group.
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fig2: Effects of aging and 1400W treatment on vascular inducible nitric oxide synthase (iNOS) immunostaining (A, DAB staining, ×40) and iNOS expression (B, Western blot). cP<0.01 vs young group; eP<0.05 vs aging group. n=7 rats per group.

Mentions: To determine the role of iNOS in aging-induced endothelium vasodilator dysfunction, firstly we observed iNOS expression by immunohistological and Western blot. As illustrated in Figure 2, compared to the young group, endothelial and smooth muscle expression of iNOS was significantly increased in vascular samples from the aged group. After treatment with the highly selective iNOS inhibitor 1400W, the expression of iNOS in the endothelial and smooth muscle was significantly decreased compared with the aged group. Then, following treatment with a highly selective iNOS inhibitor 1400W, endothelial and smooth muscle function in aged rat aortas were determined by comparing the vasorelaxation response to ACh with that of acidified NaNO2. As illustrated in Figure 1, 1400W markedly improved ACh-induced vasorelaxation (maximal relaxation: 87%±8%, P<0.05, -logEC50: 7.3±0.2, P<0.05), while having no effect on acidified NaNO2-induced vasorelaxation (maximal relaxation: 94%±3%, P>0.05, -logEC50: 6.5±0.3, P>0.05). These results demonstrated that 1400W attenuated aging-induced endothelial dysfunction.


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)

Effects of aging and 1400W treatment on vascular inducible nitric oxide synthase (iNOS) immunostaining (A, DAB staining, ×40) and iNOS expression (B, Western blot). 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

fig2: Effects of aging and 1400W treatment on vascular inducible nitric oxide synthase (iNOS) immunostaining (A, DAB staining, ×40) and iNOS expression (B, Western blot). cP<0.01 vs young group; eP<0.05 vs aging group. n=7 rats per group.
Mentions: To determine the role of iNOS in aging-induced endothelium vasodilator dysfunction, firstly we observed iNOS expression by immunohistological and Western blot. As illustrated in Figure 2, compared to the young group, endothelial and smooth muscle expression of iNOS was significantly increased in vascular samples from the aged group. After treatment with the highly selective iNOS inhibitor 1400W, the expression of iNOS in the endothelial and smooth muscle was significantly decreased compared with the aged group. Then, following treatment with a highly selective iNOS inhibitor 1400W, endothelial and smooth muscle function in aged rat aortas were determined by comparing the vasorelaxation response to ACh with that of acidified NaNO2. As illustrated in Figure 1, 1400W markedly improved ACh-induced vasorelaxation (maximal relaxation: 87%±8%, P<0.05, -logEC50: 7.3±0.2, P<0.05), while having no effect on acidified NaNO2-induced vasorelaxation (maximal relaxation: 94%±3%, P>0.05, -logEC50: 6.5±0.3, P>0.05). These results demonstrated that 1400W attenuated aging-induced endothelial dysfunction.

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