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Phosphodiesterase type 5 inhibition does not reverse endothelial dysfunction in patients with coronary heart disease
  1. S D Robinson1,
  2. C A Ludlam2,
  3. N A Boon3,
  4. D E Newby1
  1. 1Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, UK
  2. 2Department of Haematology, Royal Infirmary of Edinburgh, Edinburgh, UK
  3. 3Department of Cardiology, Royal Infirmary of Edinburgh, Edinburgh, UK
  1. Correspondence to:
    Dr Simon Robinson
    Centre for Cardiovascular Sciences, University of Edinburgh, Royal Infirmary of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK; simon.robinson{at}ed.ac.uk

Abstract

Objectives: To investigate whether sildenafil citrate, a selective phosphodiesterase type 5 inhibitor, may improve endothelial vasomotor and fibrinolytic function in patients with coronary heart disease.

Design: Randomised double blind placebo controlled crossover study.

Patients and 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.

Main outcome measures: 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.

  • cGMP, cyclic guanosine monophosphate
  • CHD, coronary heart disease
  • FBF, forearm blood flow
  • PAI-1, plasminogen activator inhibitor type 1
  • PDE5, phosphodiesterase type 5
  • t-PA, tissue plasminogen activator
  • coronary heart disease
  • endothelium
  • fibrinolysis
  • forearm blood flow
  • nitric oxide

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Footnotes

  • Published Online First 29 April 2005

  • Grant support: This work was supported by an educational award from the Sildenafil Research Grants Programme 2002, Pfizer Inc, New York, USA. Dr Robinson is the recipient of a British Heart Foundation Junior Research Fellowship (FS/2001/047).

  • Competing interests: SDR has received financial support for attending scientific meetings from Pfizer Ltd; NAB was a member of a drug advisory committee evaluating sildenafil and has received and supervised research grants from Pfizer Ltd; DEN holds unrestricted educational grant awards and has undertaken paid consultancy for Pfizer Ltd.

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