Sildenafil, a PDE5 inhibitor, in the treatment of pulmonary hypertension.
Pulmonary hypertension is a devastating disorder, characterized by vascular proliferation, intimal hypertrophy and vasoconstriction. In this disorder, alterations in the nitric oxide pathway have borne out to be important in not only vascular proliferation, but also in the maintenance of vascular tone. After synthesis by soluble guanylate cyclase, cGMP effects vasodilation via protein kinase G and other mediators, and is hydrolyzed by phosphodiesterases (PDEs). PDE5 is abundantly expressed in the mammalian lung and its inhibition by sildenafil has been demonstrated to improve pulmonary vascular physiology in vitro and in vivo animal models of pulmonary hypertension. Recent human data has confirmed the efficacy of sildenafil in therapy for humans with pulmonary arterial hypertension. The following review will discuss the underlying basic science supporting the use of sildenafil, as well as human evidence supporting the critical role of this drug in therapy of patients with pulmonary hypertension.
Hemnes
Anna R
AR
Johns Hopkins University, Johns 720 Rutland Avenue, Ross 850, Baltimore, MD 21205, USA. ahemnese@jhmi.edu
Champion
Hunter C
HC
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000959:Antihypertensive Agents / Q000627:therapeutic use; D000077300:Bosentan; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004359:Drug Therapy, Combination; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D011465:Prostaglandins, Synthetic / Q000627:therapeutic use; D011687:Purines; D000068677:Sildenafil Citrate; D013449:Sulfonamides / Q000627:therapeutic use; D013450:Sulfones
D000959:Antihypertensive Agents; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011465:Prostaglandins, Synthetic; D011687:Purines; D013449:Sulfonamides; D013450:Sulfones; D000068677:Sildenafil Citrate; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human; D000077300:Bosentan