Pharmacological preconditioning with sildenafil: Basic mechanisms and clinical implications
| Autor: | Michael Wittkamp, Chang Yin, Ramzi A Ockaili, Amit K. Kukreja, Fadi N Salloum, Xiaoyin Wang, Vijay R. Marwaha, John Hawkins, Rakesh C. Kukreja, Anindita Das, Patrick W. Fisher, Yvonne A Bremer, Lei Xi, Eric Chou |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
Phosphodiesterase Inhibitors Physiology Sildenafil Ischemia Myocardial Reperfusion Injury Vasodilation Pharmacology Piperazines Sildenafil Citrate chemistry.chemical_compound 3' 5'-Cyclic-GMP Phosphodiesterases Internal medicine Animals Humans Medicine Sulfones Endothelial dysfunction Cyclic Nucleotide Phosphodiesterases Type 5 Cardioprotection Phosphoric Diester Hydrolases business.industry Phosphodiesterase medicine.disease respiratory tract diseases chemistry Purines Ischemic Preconditioning Myocardial cardiovascular system Cardiology Molecular Medicine Ischemic preconditioning business Reperfusion injury |
| Zdroj: | Vascular Pharmacology. 42:219-232 |
| ISSN: | 1537-1891 |
| DOI: | 10.1016/j.vph.2005.02.010 |
| Popis: | The phosphodiesterase type-5 (PDE5) inhibitor, sildenafil, is the first drug developed for treatment of erectile dysfunction in patients. Experimental data in animals show that sildenafil has a preconditioning-like cardioprotective effect against ischemia/reperfusion injury in the intact heart. Mechanistic studies suggest that sildenafil exerts cardioprotection through NO generated from eNOS/iNOS, activation of protein kinase C/ERK signaling and opening of mitochondrial ATP-sensitive potassium channels. Additional studies show that the drug attenuates cell death resulting from necrosis and apoptosis, and increases the Bcl2/Bax ratio through NO signaling in adult cardiomyocytes. Emerging new data also suggest that sildenafil may be used clinically for treatment of pulmonary arterial hypertension and endothelial dysfunction. Future demonstration of the cardioprotective effect in patients with the relatively safe and effective FDA-approved PDE5 inhibitors such as sildenafil could have an enormous impact on bringing the long-studied phenomenon of ischemic and pharmacologic preconditioning to the clinical forefront. |
| Databáze: | OpenAIRE |
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