Potential role of type 5 phosphodiesterase inhibition in the treatment of congestive heart failure.
Endothelial dysfunction is associated with impairment of aerobic capacity in patients with heart failure and may play a role in the progression of disease. Impaired endothelium-dependent vasodilation in patients with heart failure can be attributed to decreased bioavailability of nitric oxide and attenuated responses to nitric oxide in vascular smooth muscle. Impaired vasodilation in response to nitric oxide derived from vascular endothelium or organic nitrates in vascular smooth muscle may be related in part to increased degradation of the second messenger cyclic guanosine monophosphate by type 5 phosphodiesterase. Sildenafil, a specific type 5 phosphodiesterase inhibitor currently approved for the treatment of erectile dysfunction, has been shown to acutely enhance endothelium-dependent vasodilation in patients with heart failure. Further studies are warranted to characterize the safety and efficacy of type 5 phosphodiesterase inhibition in the treatment of chronic heart failure.
Katz
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SD
Yale University School of Medicine, Heart Failure Center, Yale University, 135 College Street, Suite 201, New Haven, CT 06510, USA. stuart.katz@yale.edu
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006152:Cyclic GMP / Q000378:metabolism; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006162:Guanylate Cyclase / Q000187:drug effects / Q000502:physiology; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000627:therapeutic use; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects* / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014666:Vasomotor System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology
D009569:Nitric Oxide; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human; D006162:Guanylate Cyclase; D006152:Cyclic GMP