![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
RE Howell, LP Jenkins and DE Howell
Inflammatory Diseases Division, Wyeth-Ayerst Research, Princeton, New Jersey, USA.
There is a need for pharmacological agents for the treatment of pulmonary edema associated with the adult respiratory distress syndrome. Therefore, we examined the effects of isozyme-selective cyclic AMP phosphodiesterase (cAMP PDE) inhibitors, as well as aminophylline and dexamethasone, on the pulmonary edema, protein leakage into the airways and airway neutrophilia induced by aerosolized lipopolysaccharide (LPS) in intact guinea pigs. Twenty-four hours after LPS exposure lung wet/dry weight ratios increased from 4.9 +/- 0.004 to 5.8 +/- 0.02. Rolipram (PDE4 selective), CI-930 (PDE3 selective), aminophylline and dexamethasone (given p.o. 1 hr before and 4 hr after LPS exposure) inhibited pulmonary edema formation with ED50 values of 1.7, 0.5, 31 and 2.8 mg/kg, respectively. Maximum inhibition occurred with rolipram at 10 mg/kg (70 +/- 17%), CI-930 at 10 mg/kg (101 +/- 4%), aminophylline at 50 mg/kg (88 +/- 14%) and dexamethasone at 3 mg/kg (64 +/- 6%). Denbufylline and milrinone also inhibited pulmonary edema formation at 10 mg/kg i.p., supporting the inhibition of PDE4 and PDE3 as the mechanisms of action of rolipram and CI-930, respectively. Rolipram, CI-930, aminophylline and dexamethasone (at maximum doses for inhibiting pulmonary edema) inhibited the 3-fold increase in bronchoalveolar lavage albumin concentration 24 hr after LPS exposure (42 +/- 14%, 98 +/- 2%, 70 +/- 9% and 53 +/- 13%, respectively). However, none of these compounds (at maximum doses for inhibiting pulmonary edema) inhibited the corresponding 400-fold increase in lavage neutrophil counts.(ABSTRACT TRUNCATED AT 250 WORDS)
This article has been cited by other articles:
|
|
 |
|
  Y. P. de Visser, F. J. Walther, E. H. Laghmani, S. van Wijngaarden, K. Nieuwland, and G. T. M. Wagenaar Phosphodiesterase-4 inhibition attenuates pulmonary inflammation in neonatal lung injury Eur. Respir. J., March 1, 2008; 31(3): 633 - 644. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.R.M. Rocco, D.P. Momesso, R.C. Figueira, H.C. Ferreira, R.A. Cadete, A. Legora-Machado, V.L.G. Koatz, L.M. Lima, E.J. Barreiro, and W.A. Zin Therapeutic potential of a new phosphodiesterase inhibitor in acute lung injury Eur. Respir. J., July 1, 2003; 22(1): 20 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. HÄFNER and P.-G. GERMANN Additive Effects of Phosphodiesterase-4 Inhibition on Effects of rSP-C Surfactant Am. J. Respir. Crit. Care Med., May 1, 2000; 161(5): 1495 - 1500. [Abstract] [Full Text]
|
|
|
|
|
|
T. J. TORPHY Phosphodiesterase Isozymes . Molecular Targets for Novel Antiasthma Agents Am. J. Respir. Crit. Care Med., February 1, 1997; 157(2): 351 - 370. [Full Text]
|
|
|
|
 |
|
 Y. Sato, S. Sato, T. Yamamoto, S. Ishikawa, M. Onizuka, and Y. Sakakibara Phosphodiesterase type 4 inhibitor reduces the retention of polymorphonuclear leukocytes in the lung Am J Physiol Lung Cell Mol Physiol, June 1, 2002; 282(6): L1376 - L1381. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
