Type 5 phosphodiesterase inhibition in heart failure and pulmonary hypertension.
The availability of selective inhibitors of the cyclic guanosine monophosphate (cGMP)-specific type 5 phosphodiesterase (PDE5) has created increasing interest in unlocking the therapeutic potential of PDE5 inhibition in cardiovascular diseases that are marked by dysfunction of nitric oxide (NO)-cGMP signaling. Pulmonary arterial hypertension (PAH) and heart failure (HF) are characterized by pulmonary arterial vasoconstriction that is thought to be caused by relative deficiencies of vasodilators such as NO and exaggerated production of vasoconstrictors such as endothelin. PDE5 is abundant in the pulmonary vasculature where it catabolizes cGMP, the second messenger of NO. Inhibition of PDE5 has been shown to lower pulmonary vascular resistance in PAH and HF by augmenting local cGMP. This review outlines the therapeutic potential of PDE5 inhibition for the treatment of PAH and HF.
Lewis
Gregory D
GD
Cardiology Division, Bigelow 800, Massachusetts General Hospital, Fruit Street, Boston, MA 02114, USA.
Semigran
Marc J
MJ
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D009569:Nitric Oxide / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D010727:Phosphoric Diester Hydrolases; D010879:Piperazines / Q000627:therapeutic use; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D009569:Nitric Oxide; D000068677:Sildenafil Citrate; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human; D006152:Cyclic GMP