Effect of Phosphodiesterase-5 Inhibitor, Sildenafil (Viagra), in Animal Models of Airways Disease

American Journal of Respiratory and Critical Care Medicine

Volumn 169, Issue 2, 2004, Pages 227-234

  Toward, Toby J ^a   Smith, Nicola ^a   Broadley, Kenneth J ^a  

^a CARDIFF UNIVERSITY   (United Kingdom)

Author keywords

Airway hyperreactivity; Asthma; Inflammation; LPS; Phosphodiesterase 5 inhibitor; Viagra

Indexed keywords

CYCLIC GMP; HISTAMINE; LIPOPOLYSACCHARIDE; N ACETYL S NITROSOPENICILLAMINE; N(G) NITROARGININE METHYL ESTER; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; OVALBUMIN; PHOSPHODIESTERASE V; PHOSPHODIESTERASE V INHIBITOR; SILDENAFIL;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; ATOPY; BODY PLETHYSMOGRAPHY; BRONCHOSPASM; BRONCHUS HYPERREACTIVITY; CELL COUNT; CONSCIOUSNESS; CONTROLLED STUDY; DISEASE MODEL; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; ENZYME INHIBITION; EOSINOPHIL; GUINEA PIG; INHALATION; ISOLATED LUNG; LEUKOCYTE MIGRATION INHIBITION; LUNG LAVAGE; MACROPHAGE; MALE; NONHUMAN; PRIORITY JOURNAL; RESPIRATORY TRACT INFLAMMATION; SENSITIZATION;

AIRWAY RESISTANCE; ALLERGENS; ANIMALS; ASTHMA; BRONCHIAL HYPERREACTIVITY; BRONCHOALVEOLAR LAVAGE FLUID; CYCLIC GMP; EOSINOPHILS; GUINEA PIGS; HISTAMINE; LIPOPOLYSACCHARIDES; LUNG; MACROPHAGES; MALE; NG-NITROARGININE METHYL ESTER; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; OVALBUMIN; PHOSPHODIESTERASE INHIBITORS; PIPERAZINES;

EID: 1642493925     PISSN: 1073449X     EISSN: None     Source Type: Journal    
DOI: 10.1164/rccm.200211-1372OC     Document Type: Article

References (39)

1. Bivalacqua TJ, Champion HC, Hellstrom WJG, Kadowitz PJ. Pharmacotherapy for erectile dysfunction. Trends Pharmacol Sci 2000;21:484-489.
2. Raeburn D, Souness JE, Tomkinson A, Karlsson J-A. Isoenzyme-selective cyclic nucleotide phosphodiesterase inhibitors: biochemistry, pharmacology and therapeutic potential in asthma. Prog Drug Res 1993;40:9-32.
3. Nijkamp FP, Folkerts G. Nitric oxide and bronchial hyperresponsiveness. Arch Int Pharmacodyn Ther 1995;329:81-96.
4. Pelligrino DA, Wang Q. Cyclic nucleotide cross-talk and the regulation of cerebral vasodilation. Prog Neurobiol 1998;56:1-18.
5. Postma DS, Kerstjens HAM. Characteristics of airway hyperresponsiveness in asthma and chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;15:S187-S192.
6. Saleh DA, Ernst P, Lim S, Barnes P, Giaid A. Increased formation of the potent oxidant peroxynitrite in the airways of asthmatic patients is associated with the induction of nitric oxide synthase: effect of inhaled glucocorticoidsteroids. FASEB J 1998;12:929-937.
7. Agusti AGN, Vilaverde JM, Togores B, Bosch M. Serial measurements of exhaled nitric oxide during exacerbations of chronic obstructive pulmonary disease. Eur Respir J 1999;14:523-528.
8. Torphy TJ. β-adrenoceptors, cAMP and airway smooth muscle relaxation: challenges to the dogma. Trends Pharmacol Sci 1994;15:370-374.
9. Danahay H, Broadley KJ. Effects of inhibitors of phosphodiesterase, on antigen-induced bronchial hyperreactivity in conscious sensitised guinea-pigs and airway leukocyte infiltration. Br J Pharmacol 1997;120: 289-297.
10. Toward TJ, Broadley KJ. Chronic lipopolysaccharide exposure on airway function, cell infiltration, and nitric oxide generation in conscious guinea pigs: effect of rolipram and dexamethasone. J Pharmacol Exp Ther 2001;298:298-306.
11. Toward TJ, Broadley KJ. Airway function, hyperreactivity, cell influx and nitric oxide, in conscious parainfluenza-3 virus infected guinea-pigs: effects of dexamethasone and rolipram. Br J Pharmacol 2001;135:P54.
12. Toward TJ, Broadley KJ. Goblet cell hyperplasia, airway function and leukocyte infiltration after chronic LPS exposure in conscious guinea-pigs: effects of rolipram and dexamethasone. J Pharmacol Exp Ther 2002; 302:814-821.
13. Ortiz JL, Valles JM, Marti-Cabrera M, Cortijo J, Morcillo EJ. Effects of selective phosphodiesterase inhibitors on platelet-activating factor-and antigen-induced airways hyperreactivity, eosinophil accumulation, and microvascular leakage in guinea pigs. Naunyn Schmiedebergs Arch Pharmacol 1996;353:200-206.
14. Kanehiro A, Ikemura T, Makela MJ, Lahn M, Joetham A, Dakhama A, Gelfand EW. Inhibition of phosphodiesterase 4 attenuates airway hyperresponsiveness and airway inflammation in a model of secondary allergen challenge. Am J Respir Crit Care Med 2001;163:173-184.
15. Santing RE, Olymulder CG, Van der Molen K, Meurs H, Zaagsma J. Phospodiesterase inhibitors reduce bronchial hyperreactivity and airway inflammation in unrestrained guinea pigs. Eur J Pharmacol 1995; 275:75-82.
16. Santing RE, de Boer J, Rohof A, van der Zee NM, Zaagsma J. Bronchodilatory and anti-inflammatory properties of inhaled selective phosphodiesterase inhibitors in a guinea pig model of allergic asthma. Eur J Pharmacol 2001;429:335-344.
17. Bousquet J, Jeffery PK, Busse WW, Johnson M, Vignola AM. Asthma: from bronchoconstriction to airways inflammation and remodelling. Am J Respir Crit Care Med 1999;161:1720-1745.
18. Gamble E, Grootendorst DC, Brightling CE, Troy S, Qui Y, Zhu J, Parker D, Vignola AM, Kroegel C, Morell F, et al. Anti-inflammatory effects of the phosphodiesterase 4 inhibitor cilomilast (Ariflo) in COPD. Am J Respir Crit Care Med (In press).
19. Torphy TJ, Barnette MS, Underwood DC, Griswold DE, Christensen SB, Murdoch RD, Nieman RB, Compton CH. Ariflo (SB 207499), a second generation phosphodiesterase 4 inhibitor for the treatment of asthma and COPD: from concept to clinic. Pulm Pharmacol Ther 1999; 12:131-135.
20. Fuhrmann M, Jahn HU, Seybold J, Neurohr C, Barnes PJ, Hippenstiel S, Kraemer HJ, Suttorp N. Identification and function of cyclic nucleotide phosphodiesterase isoenzymes in airway epithelial cells. Am J Respir Cell Mol Biol 1999;20:292-302.
21. Frossard N, Landry Y, Pauli G, Ruckstuhl M. Effects of cyclic AMP-and GMP-phosphodiesterases on immunological release of histamine and on lung contraction. Br J Pharmacol 1981;73:933-938.
22. Ballard SA, Gingell CJ, Tang K, Price ME, Naylor AM. Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes. J Urol 1998;159:2164-2171.
23. Toward TJ, Broadley, KJ. Airway reactivity, inflammatory cell influx and nitric oxide in guinea-pig airways after lipopolysaccharide inhalation. Br J Pharmacol 2000;131:271-281.
24. Toward TJ, Broadley KJ. Lung nitric oxide, histamine and leukocyte influx in sensitised guinea-pigs after antigen inhalation: relation to EAR, LAR and AHR: Proceedings from the Pharmacology 2001 Meeting (Vancouver). Br J Pharmacol 2001;133:P262.
25. Griffiths-Johnson DA, Nicholls PJ, McDermott M. Measurement of specific airways conductance in guinea-pigs: a non-invasive method. J Pharmacol Methods 1988;19:233-242.
26. Goldenberg MM. Safety and efficacy of sildenafil citrate in the treatment of male erectile dysfunction. Clin Ther 1998;20:1033-1048.
27. Schuiling M, Zuidhof AB, Bonouvrie MAA, Venema N, Zaagsma J, Meurs H. Role of nitric oxide in the development and partial reversal of allergen-induced airway hyperreactivity in conscious, unrestrained guinea-pigs. Br J Pharmacol 1998;123:1450-1456.
28. Grisham MB, Johnson GG, Lancaster JR. Quantification of nitrate and nitrite in extracellular fluids. Methods Enzymol 1996;268:237-246.
29. Rafferty P, Beasley R, Holgate ST. The contribution of histamine to immediate bronchoconstriction provoked by inhaled antigen and adenosine 5′-monophosphate in atopic asthma. Am Rev Respir Dis 1987;136: 369-373.
30. Torphy TJ, Page CP. Phosphodiesterases: the journey towards therapeutics. Trends Pharmacol Sci 2000;21:157-159.
31. Barnes PJ, Chung KF, Page CP. Inflammatory mediators of asthma: an update. Pharmacol Rev 1999;50:515-575.
32. Kubes P, Suzuki M, Granger DN. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci USA 1991;88:4651-4655.
33. Colasanti M, Suzuki H. The dual personality of NO. Trends Pharmacol Sci 2000;21:249-252.
34. Ichinose M, Sugiura H, Yamagata S, Koarai A, Shirato K. Increase in reactive nitrogen species production in chronic obstructive pulmonary disease airways. Am J Respir Crit Care Med 2000;162:701-706.
35. Brigham KL, Meyrick B. Endotoxin and lung injury. Am Rev Respir Dis 1986;133:913-927.
36. Kips JC, Tavernier J, Pauwels RA. Tumour necrosis factor causes bronchial hyperresponsiveness in rats. Am Rev Respir Dis 1992;145:332-336.
37. Toward TJ, Broadley KJ. Airway function, oedema, cell infiltration and nitric oxide generation in conscious ozone-exposed guinea-pigs: effects of dexamethasone and rolipram. Br J Pharmacol 2002;136:735-745.
38. Toward TJ, Broadley KJ. Adenylyl and guanylyl cyclase and PDE activities toward cAMP and cGMP in isolated guinea-pig lungs during LPS-induced airway reactivity change. Br J Pharmacol 2001;135:P54.
39. Allegra L, Blasi F, Bucchioni E, Centanni S, Raiteri L, Fasano V. Bronchoprotective activity of sildenafil (Viagra) in asthmatics: Proceedings from the 11th European Respiratory Society Annual Congress. Eur Respir J 2001;18:P2892.