Heme Oxygenase-1 Induction and Organic Nitrate Therapy: Beneficial Effects on Endothelial Dysfunction, Nitrate Tolerance, and Vascular Oxidative Stress
Organic nitrates are a group of very effective anti-ischemic drugs. They are used for the treatment of patients with stable angina, acute myocardial infarction, and chronic congestive heart failure. A major therapeutic limitation inherent to organic nitrates is the development of tolerance, which oc...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | International Journal of Hypertension |
| Online Access: | http://dx.doi.org/10.1155/2012/842632 |
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| author | Andreas Daiber Matthias Oelze Philip Wenzel Franziska Bollmann Andrea Pautz Hartmut Kleinert |
| author_facet | Andreas Daiber Matthias Oelze Philip Wenzel Franziska Bollmann Andrea Pautz Hartmut Kleinert |
| author_sort | Andreas Daiber |
| collection | DOAJ |
| description | Organic nitrates are a group of very effective anti-ischemic drugs. They are used for the treatment of patients with stable angina, acute myocardial infarction, and chronic congestive heart failure. A major therapeutic limitation inherent to organic nitrates is the development of tolerance, which occurs during chronic treatment with these agents, and this phenomenon is largely based on induction of oxidative stress with subsequent endothelial dysfunction. We therefore speculated that induction of heme oxygenase-1 (HO-1) could be an efficient strategy to overcome nitrate tolerance and the associated side effects. Indeed, we found that hemin cotreatment prevented the development of nitrate tolerance and vascular oxidative stress in response to chronic nitroglycerin therapy. Vice versa, pentaerithrityl tetranitrate (PETN), a nitrate that was previously reported to be devoid of adverse side effects, displayed tolerance and oxidative stress when the HO-1 pathway was blocked pharmacologically or genetically by using HO-1+/– mice. Recently, we identified activation of Nrf2 and HuR as a principle mechanism of HO-1 induction by PETN. With the present paper, we present and discuss our recent and previous findings on the role of HO-1 for the prevention of nitroglycerin-induced nitrate tolerance and for the beneficial effects of PETN therapy. |
| format | Article |
| id | doaj-art-bf8eb2f524c4468d9ba4a5eed9b4af90 |
| institution | OA Journals |
| issn | 2090-0384 2090-0392 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Hypertension |
| spelling | doaj-art-bf8eb2f524c4468d9ba4a5eed9b4af902025-08-20T02:19:26ZengWileyInternational Journal of Hypertension2090-03842090-03922012-01-01201210.1155/2012/842632842632Heme Oxygenase-1 Induction and Organic Nitrate Therapy: Beneficial Effects on Endothelial Dysfunction, Nitrate Tolerance, and Vascular Oxidative StressAndreas Daiber0Matthias Oelze1Philip Wenzel2Franziska Bollmann3Andrea Pautz4Hartmut Kleinert52nd Medical Clinic, Department of Cardiology, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany2nd Medical Clinic, Department of Cardiology, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany2nd Medical Clinic, Department of Cardiology, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, GermanyDepartment of Pharmacology, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, GermanyDepartment of Pharmacology, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, GermanyDepartment of Pharmacology, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, GermanyOrganic nitrates are a group of very effective anti-ischemic drugs. They are used for the treatment of patients with stable angina, acute myocardial infarction, and chronic congestive heart failure. A major therapeutic limitation inherent to organic nitrates is the development of tolerance, which occurs during chronic treatment with these agents, and this phenomenon is largely based on induction of oxidative stress with subsequent endothelial dysfunction. We therefore speculated that induction of heme oxygenase-1 (HO-1) could be an efficient strategy to overcome nitrate tolerance and the associated side effects. Indeed, we found that hemin cotreatment prevented the development of nitrate tolerance and vascular oxidative stress in response to chronic nitroglycerin therapy. Vice versa, pentaerithrityl tetranitrate (PETN), a nitrate that was previously reported to be devoid of adverse side effects, displayed tolerance and oxidative stress when the HO-1 pathway was blocked pharmacologically or genetically by using HO-1+/– mice. Recently, we identified activation of Nrf2 and HuR as a principle mechanism of HO-1 induction by PETN. With the present paper, we present and discuss our recent and previous findings on the role of HO-1 for the prevention of nitroglycerin-induced nitrate tolerance and for the beneficial effects of PETN therapy.http://dx.doi.org/10.1155/2012/842632 |
| spellingShingle | Andreas Daiber Matthias Oelze Philip Wenzel Franziska Bollmann Andrea Pautz Hartmut Kleinert Heme Oxygenase-1 Induction and Organic Nitrate Therapy: Beneficial Effects on Endothelial Dysfunction, Nitrate Tolerance, and Vascular Oxidative Stress International Journal of Hypertension |
| title | Heme Oxygenase-1 Induction and Organic Nitrate Therapy: Beneficial Effects on Endothelial Dysfunction, Nitrate Tolerance, and Vascular Oxidative Stress |
| title_full | Heme Oxygenase-1 Induction and Organic Nitrate Therapy: Beneficial Effects on Endothelial Dysfunction, Nitrate Tolerance, and Vascular Oxidative Stress |
| title_fullStr | Heme Oxygenase-1 Induction and Organic Nitrate Therapy: Beneficial Effects on Endothelial Dysfunction, Nitrate Tolerance, and Vascular Oxidative Stress |
| title_full_unstemmed | Heme Oxygenase-1 Induction and Organic Nitrate Therapy: Beneficial Effects on Endothelial Dysfunction, Nitrate Tolerance, and Vascular Oxidative Stress |
| title_short | Heme Oxygenase-1 Induction and Organic Nitrate Therapy: Beneficial Effects on Endothelial Dysfunction, Nitrate Tolerance, and Vascular Oxidative Stress |
| title_sort | heme oxygenase 1 induction and organic nitrate therapy beneficial effects on endothelial dysfunction nitrate tolerance and vascular oxidative stress |
| url | http://dx.doi.org/10.1155/2012/842632 |
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