Sildenafil restores endothelial function in the apolipoprotein E knockout mouse
<p>Abstract</p> <p>Background</p> <p>Atherosclerosis is an inflammatory process of the arterial walls and is initiated by endothelial dysfunction accompanied by an imbalance in the production of reactive oxygen species (ROS) and nitric oxide (NO). Sildenafil, a selectiv...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2013-01-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | http://www.translational-medicine.com/content/11/1/3 |
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| author | Balarini Camille M Leal Marcos A Gomes Isabele B S Pereira Thiago M C Gava Agata L Meyrelles Silvana S Vasquez Elisardo C |
| author_facet | Balarini Camille M Leal Marcos A Gomes Isabele B S Pereira Thiago M C Gava Agata L Meyrelles Silvana S Vasquez Elisardo C |
| author_sort | Balarini Camille M |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Atherosclerosis is an inflammatory process of the arterial walls and is initiated by endothelial dysfunction accompanied by an imbalance in the production of reactive oxygen species (ROS) and nitric oxide (NO). Sildenafil, a selective phosphodiesterase-5 (PDE5) inhibitor used for erectile dysfunction, exerts its cardiovascular effects by enhancing the effects of NO. The aim of this study was to investigate the influence of sildenafil on endothelial function and atherosclerosis progression in apolipoprotein E knockout (apoE<sup>−/−</sup>) mice.</p> <p>Methods</p> <p>ApoE<sup>−/−</sup> mice treated with sildenafil (Viagra®, 40 mg/kg/day, for 3 weeks, by oral gavage) were compared to the untreated apoE<sup>−/−</sup> and the wild-type (WT) mice.</p> <p>Aortic rings were used to evaluate the relaxation responses to acetylcholine (ACh) in all of the groups. In a separate set of experiments, the roles of NO and ROS in the relaxation response to ACh were evaluated by incubating the aortic rings with L-NAME (NO synthase inhibitor) or apocynin (NADPH oxidase inhibitor). In addition, the atherosclerotic lesions were quantified and superoxide production was assessed.</p> <p>Results</p> <p>Sildenafil restored the vasodilator response to acetylcholine (ACh) in the aortic rings of the apoE<sup>−/−</sup> mice. Treatment with L-NAME abolished the vasodilator responses to ACh in all three groups of mice and revealed an augmented participation of NO in the endothelium-dependent vasodilation in the sildenafil-treated animals. The normalized endothelial function in sildenafil-treated apoE<sup>−/−</sup> mice was unaffected by apocynin highlighting the low levels of ROS production in these animals. Moreover, morphological analysis showed that sildenafil treatment caused approximately a 40% decrease in plaque deposition in the aorta.</p> <p>Conclusion</p> <p>This is the first study demonstrating the beneficial effects of chronic treatment with sildenafil on endothelial dysfunction and atherosclerosis in a model of spontaneous hypercholesterolemia. These data indicate that the main mechanism of the beneficial effect of sildenafil on the endothelial function appears to involve an enhancement of the NO pathway along with a reduction in oxidative stress.</p> |
| first_indexed | 2024-12-18T05:40:09Z |
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| id | doaj.art-b4e4e645cff544428a8b461c1aa93ab6 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-18T05:40:09Z |
| publishDate | 2013-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-b4e4e645cff544428a8b461c1aa93ab62022-12-21T21:19:11ZengBMCJournal of Translational Medicine1479-58762013-01-01111310.1186/1479-5876-11-3Sildenafil restores endothelial function in the apolipoprotein E knockout mouseBalarini Camille MLeal Marcos AGomes Isabele B SPereira Thiago M CGava Agata LMeyrelles Silvana SVasquez Elisardo C<p>Abstract</p> <p>Background</p> <p>Atherosclerosis is an inflammatory process of the arterial walls and is initiated by endothelial dysfunction accompanied by an imbalance in the production of reactive oxygen species (ROS) and nitric oxide (NO). Sildenafil, a selective phosphodiesterase-5 (PDE5) inhibitor used for erectile dysfunction, exerts its cardiovascular effects by enhancing the effects of NO. The aim of this study was to investigate the influence of sildenafil on endothelial function and atherosclerosis progression in apolipoprotein E knockout (apoE<sup>−/−</sup>) mice.</p> <p>Methods</p> <p>ApoE<sup>−/−</sup> mice treated with sildenafil (Viagra®, 40 mg/kg/day, for 3 weeks, by oral gavage) were compared to the untreated apoE<sup>−/−</sup> and the wild-type (WT) mice.</p> <p>Aortic rings were used to evaluate the relaxation responses to acetylcholine (ACh) in all of the groups. In a separate set of experiments, the roles of NO and ROS in the relaxation response to ACh were evaluated by incubating the aortic rings with L-NAME (NO synthase inhibitor) or apocynin (NADPH oxidase inhibitor). In addition, the atherosclerotic lesions were quantified and superoxide production was assessed.</p> <p>Results</p> <p>Sildenafil restored the vasodilator response to acetylcholine (ACh) in the aortic rings of the apoE<sup>−/−</sup> mice. Treatment with L-NAME abolished the vasodilator responses to ACh in all three groups of mice and revealed an augmented participation of NO in the endothelium-dependent vasodilation in the sildenafil-treated animals. The normalized endothelial function in sildenafil-treated apoE<sup>−/−</sup> mice was unaffected by apocynin highlighting the low levels of ROS production in these animals. Moreover, morphological analysis showed that sildenafil treatment caused approximately a 40% decrease in plaque deposition in the aorta.</p> <p>Conclusion</p> <p>This is the first study demonstrating the beneficial effects of chronic treatment with sildenafil on endothelial dysfunction and atherosclerosis in a model of spontaneous hypercholesterolemia. These data indicate that the main mechanism of the beneficial effect of sildenafil on the endothelial function appears to involve an enhancement of the NO pathway along with a reduction in oxidative stress.</p>http://www.translational-medicine.com/content/11/1/3AtherosclerosisApoE knockout miceSildenafilNitric oxideOxidative stressEndothelial dysfunctionPDE5cGMP |
| spellingShingle | Balarini Camille M Leal Marcos A Gomes Isabele B S Pereira Thiago M C Gava Agata L Meyrelles Silvana S Vasquez Elisardo C Sildenafil restores endothelial function in the apolipoprotein E knockout mouse Journal of Translational Medicine Atherosclerosis ApoE knockout mice Sildenafil Nitric oxide Oxidative stress Endothelial dysfunction PDE5 cGMP |
| title | Sildenafil restores endothelial function in the apolipoprotein E knockout mouse |
| title_full | Sildenafil restores endothelial function in the apolipoprotein E knockout mouse |
| title_fullStr | Sildenafil restores endothelial function in the apolipoprotein E knockout mouse |
| title_full_unstemmed | Sildenafil restores endothelial function in the apolipoprotein E knockout mouse |
| title_short | Sildenafil restores endothelial function in the apolipoprotein E knockout mouse |
| title_sort | sildenafil restores endothelial function in the apolipoprotein e knockout mouse |
| topic | Atherosclerosis ApoE knockout mice Sildenafil Nitric oxide Oxidative stress Endothelial dysfunction PDE5 cGMP |
| url | http://www.translational-medicine.com/content/11/1/3 |
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