Phosphodiesterase type 5 inhibition does not reverse endothelial dysfunction in patients with coronary heart disease.
OBJECTIVE
To investigate whether sildenafil citrate, a selective phosphodiesterase type 5 inhibitor, may improve endothelial vasomotor and fibrinolytic function in patients with coronary heart disease.


METHODS
Randomised double blind placebo controlled crossover study.


METHODS
16 male patients with coronary heart disease and eight matched healthy men received intravenous sildenafil or placebo. Bilateral forearm blood flow and fibrinolytic parameters were measured by venous occlusion plethysmography and blood sampling in response to intrabrachial infusions of acetylcholine, substance P, sodium nitroprusside, and verapamil.


METHODS
Forearm blood flow and acute release of tissue plasminogen activator.


RESULTS
Mean arterial blood pressure fell during sildenafil infusion from a mean (SEM) of 92 (1) to 82 (1) mm Hg in patients and from 94 (1) to 82 (1) mm Hg in controls (p < 0.001 for both). Sildenafil increased endothelium independent vasodilatation with sodium nitroprusside (p < 0.05) but did not alter the blood flow response to acetylcholine or verapamil in patients or controls. Substance P caused a dose dependent increase in plasma tissue plasminogen activator antigen concentrations (p < 0.01) that was unaffected by sildenafil in either group.


CONCLUSIONS
Sildenafil does not improve peripheral endothelium dependent vasomotor or fibrinolytic function in patients with coronary heart disease. Phosphodiesterase type 5 inhibitors are unlikely to reverse the generalised vascular dysfunction seen in patients with coronary heart disease.
Robinson
S D
SD
Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK. simon.robinson@ed.ac.uk
Ludlam
C A
CA
Boon
N A
NA
Newby
D E
DE
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D018592:Cross-Over Studies; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005342:Fibrinolysis / Q000187:drug effects; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010727:Phosphoric Diester Hydrolases; D010879:Piperazines / Q000627:therapeutic use*; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D010959:Tissue Plasminogen Activator / Q000378:metabolism
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human; D010959:Tissue Plasminogen Activator