Cardiovascular protection with sildenafil following chronic inhibition of nitric oxide synthase.
During the past 18 years, sildenafil has evolved from a potential anti-angina drug to an on-demand treatment for erectile dysfunction and more recently to a new orally active treatment for pulmonary hypertension. Recent studies suggest that the drug has powerful cardioprotective effect against ischemia/reperfusion injury, doxorubicin-induced cardiomyopathy and anti-hypertensive effect induced by chronic inhibition of nitric oxide synthase in animals. Based on several recent basic and clinical studies, it is clear that sildenafil and other clinically approved type-5 phosphodiesterase-5 inhibitors including vardenafil and tadalafil will eventually be developed for several cardiovascular indications including essential hypertension, endothelial dysfunction, ischemia/reperfusion injury, myocardial infarction, ventricular remodeling and heart failure.
Kukreja
R C
RC
Department of Internal Medicine, Division of Cardiology, Virginia Commonwealth University, Richmond, VA 23298, USA. rakesh@hsc.vcu.edu
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology; D009202:Cardiomyopathies / Q000139:chemically induced / Q000517:prevention & control; D002317:Cardiovascular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004195:Disease Models, Animal; D004317:Doxorubicin; D004730:Endothelium, Vascular / Q000187:drug effects; D004791:Enzyme Inhibitors; D007172:Erectile Dysfunction / Q000188:drug therapy; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D006976:Hypertension, Pulmonary / Q000188:drug therapy; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy; D015428:Myocardial Reperfusion Injury / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology* / Q000627:therapeutic use; D000068581:Tadalafil; D014227:Triazines / Q000494:pharmacology; D000069058:Vardenafil Dihydrochloride; D014665:Vasodilator Agents / Q000494:pharmacology; D020257:Ventricular Remodeling / Q000187:drug effects
D000959:Antihypertensive Agents; D002243:Carbolines; D002317:Cardiovascular Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014227:Triazines; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000069058:Vardenafil Dihydrochloride; D000068581:Tadalafil; D004317:Doxorubicin; D000068677:Sildenafil Citrate; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human; D019331:NG-Nitroarginine Methyl Ester