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. 1992 Apr;105(4):831–838. doi: 10.1111/j.1476-5381.1992.tb09065.x

Inhibition by salmeterol of increased vascular permeability and granulocyte accumulation in guinea-pig lung and skin.

C J Whelan 1, M Johnson 1
PMCID: PMC1908715  PMID: 1354536

Abstract

1. The long-acting beta 2-adrenoceptor agonist, salmeterol has been evaluated for its anti-inflammatory effects in the guinea-pig lung and skin. 2. Salmeterol, administered in bronchodilator doses to conscious guinea-pigs by both oral (0.01-1.0 mg kg-1) and inhaled (nebulizer concentration, 0.001-1.0 mg ml-1) routes, inhibited histamine-induced plasma protein extravasation (PPE) into the airway lumen. 3. Inhibition of PPE by salmeterol was long-lasting (greater than 6 h) and was inhibited by prior administration of propranolol (1 mg kg-1, s.c.), indicating an effect mediated by beta-adrenoceptors. 4. Inhaled salbutamol (nebulizer concentration, 0.001-1.0 mg ml-1) also inhibited PPE in guinea-pig lung but, in contrast to salmeterol, this effect was short-lived with substantial loss of activity 2 h after administration. 5. Inhaled salmeterol (0.1 mg ml-1) and salbutamol (1.0 mg ml-1) inhibited the accumulation of neutrophils in guinea-pig lung in response to lipopolysaccharide (100 micrograms ml-1). Salmeterol, but not salbutamol, inhibited the infiltration of eosinophils into the airway lumen in response to platelet activating factor (100 micrograms ml-1). These effects of salmeterol were blocked by prior administration of propranolol (5 mg kg-1, s.c.), indicating that they were also beta-adrenoceptor-mediated. 6. Oral salmeterol (10 mg kg-1, p.o.), but not salbutamol (10 and 100 mg kg-1, p.o.), inhibited zymosan-induced granulocyte accumulation and PPE in guinea-pig skin. Lower doses of salmeterol (0.1 and 1 mg kg-1) inhibited PPE, but not granulocyte accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adamski S. W., Langone J. J., Grega G. J. Modulation of macromolecular permeability by immune-complexes and a beta-adrenoceptor stimulant. Am J Physiol. 1987 Dec;253(6 Pt 2):H1586–H1595. doi: 10.1152/ajpheart.1987.253.6.H1586. [DOI] [PubMed] [Google Scholar]
  2. Archer C. B., MacDonald D. M. Treatment of atopic dermatitis with salbutamol. Clin Exp Dermatol. 1987 Sep;12(5):323–325. doi: 10.1111/j.1365-2230.1987.tb02500.x. [DOI] [PubMed] [Google Scholar]
  3. Arntzen F. C., Briseid K. Inhibition of carrageenin-induced rat paw oedema by catecholamines and amine-depleting drugs. Acta Pharmacol Toxicol (Copenh) 1973;32(3):179–192. doi: 10.1111/j.1600-0773.1973.tb01462.x. [DOI] [PubMed] [Google Scholar]
  4. Ball D. I., Brittain R. T., Coleman R. A., Denyer L. H., Jack D., Johnson M., Lunts L. H., Nials A. T., Sheldrick K. E., Skidmore I. F. Salmeterol, a novel, long-acting beta 2-adrenoceptor agonist: characterization of pharmacological activity in vitro and in vivo. Br J Pharmacol. 1991 Nov;104(3):665–671. doi: 10.1111/j.1476-5381.1991.tb12486.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barnes P. J., Chung K. F., Page C. P. Inflammatory mediators and asthma. Pharmacol Rev. 1988 Mar;40(1):49–84. [PubMed] [Google Scholar]
  6. Basran G. S., Paul W., Morley J., Turner-Warwick M. Adrenoceptor-agonist inhibition of the histamine-induced cutaneous response in man. Br J Dermatol. 1982 Nov;107 (Suppl 23):140–142. doi: 10.1111/j.1365-2133.1982.tb01046.x. [DOI] [PubMed] [Google Scholar]
  7. Beasley R., Roche W. R., Roberts J. A., Holgate S. T. Cellular events in the bronchi in mild asthma and after bronchial provocation. Am Rev Respir Dis. 1989 Mar;139(3):806–817. doi: 10.1164/ajrccm/139.3.806. [DOI] [PubMed] [Google Scholar]
  8. Bonnet J., Loiseau A. M., Orvoen M., Bessin P. Platelet-activating factor acether (PAF-acether) involvement in acute inflammatory and pain processes. Agents Actions. 1981 Dec;11(6-7):559–562. doi: 10.1007/BF01978740. [DOI] [PubMed] [Google Scholar]
  9. Busse W. W., Sosman J. M. Isoproterenol inhibition of isolated human neutrophil function. J Allergy Clin Immunol. 1984 Mar;73(3):404–410. doi: 10.1016/0091-6749(84)90416-0. [DOI] [PubMed] [Google Scholar]
  10. Butchers P. R., Skidmore I. F., Vardey C. J., Wheeldon A. Characterization of the receptor mediating the antianaphylactic effects of beta-adrenoceptor agonists in human lung tissue in vitro. Br J Pharmacol. 1980;71(2):663–667. doi: 10.1111/j.1476-5381.1980.tb10987.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Butchers P. R., Vardey C. J., Johnson M. Salmeterol: a potent and long-acting inhibitor of inflammatory mediator release from human lung. Br J Pharmacol. 1991 Nov;104(3):672–676. doi: 10.1111/j.1476-5381.1991.tb12487.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cockcroft D. W., Murdock K. Y. Comparative effects of inhaled salbutamol, sodium cromoglycate, and beclomethasone dipropionate on allergen-induced early asthmatic responses, late asthmatic responses, and increased bronchial responsiveness to histamine. J Allergy Clin Immunol. 1987 May;79(5):734–740. doi: 10.1016/0091-6749(87)90204-1. [DOI] [PubMed] [Google Scholar]
  13. DUNNILL M. S. The pathology of asthma, with special reference to changes in the bronchial mucosa. J Clin Pathol. 1960 Jan;13:27–33. doi: 10.1136/jcp.13.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Daly M. J., Flook J. J., Levy G. P. The selectivity of beta-adrenoceptor antagonists on cardiovascular and bronchodilator responses to isoprenaline in the anaesthetized dog. Br J Pharmacol. 1975 Feb;53(2):173–181. doi: 10.1111/j.1476-5381.1975.tb07347.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Djukanović R., Roche W. R., Wilson J. W., Beasley C. R., Twentyman O. P., Howarth R. H., Holgate S. T. Mucosal inflammation in asthma. Am Rev Respir Dis. 1990 Aug;142(2):434–457. doi: 10.1164/ajrccm/142.2.434. [DOI] [PubMed] [Google Scholar]
  16. Folkerts G., Henricks P. A., Nijkamp F. P. Inflammatory reactions in the respiratory airways of the guinea pig do not necessarily induce bronchial hyperreactivity. Agents Actions. 1988 Feb;23(1-2):94–96. doi: 10.1007/BF01967201. [DOI] [PubMed] [Google Scholar]
  17. Green K. L. The anti-inflammatory effect of catecholamines in the peritoneal cavity and hind paw of the mouse. Br J Pharmacol. 1972 Jun;45(2):322–332. doi: 10.1111/j.1476-5381.1972.tb08086.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Grega G. J., Adamski S. W. The role of venular endothelial cells in the regulation of macromolecular permeability. Microcirc Endothelium Lymphatics. 1988 Apr;4(2):143–167. [PubMed] [Google Scholar]
  19. Grega G. J., Maciejko J. J., Raymond R. M., Sak D. P. The interrelationship among histamine, various vasoactive substances, and macromolecular permeability in the canine forelimb. Circ Res. 1980 Feb;46(2):264–275. doi: 10.1161/01.res.46.2.264. [DOI] [PubMed] [Google Scholar]
  20. Gudgeon J. R., Martin W. Modulation of arterial endothelial permeability: studies on an in vitro model. Br J Pharmacol. 1989 Dec;98(4):1267–1274. doi: 10.1111/j.1476-5381.1989.tb12673.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Haddy F. J., Scott J. B., Grega G. J. Peripheral circulation: fluid transfer across the microvascular membrane. Int Rev Physiol. 1976;9:63–109. [PubMed] [Google Scholar]
  22. Horn B. R., Robin E. D., Theodore J., Van Kessel A. Total eosinophil counts in the management of bronchial asthma. N Engl J Med. 1975 May 29;292(22):1152–1155. doi: 10.1056/NEJM197505292922204. [DOI] [PubMed] [Google Scholar]
  23. Howarth P. H., Durham S. R., Lee T. H., Kay A. B., Church M. K., Holgate S. T. Influence of albuterol, cromolyn sodium and ipratropium bromide on the airway and circulating mediator responses to allergen bronchial provocation in asthma. Am Rev Respir Dis. 1985 Nov;132(5):986–992. doi: 10.1164/arrd.1985.132.5.986. [DOI] [PubMed] [Google Scholar]
  24. Hutson P. A., Holgate S. T., Church M. K. The effect of cromolyn sodium and albuterol on early and late phase bronchoconstriction and airway leukocyte infiltration after allergen challenge of nonanesthetized guinea pigs. Am Rev Respir Dis. 1988 Nov;138(5):1157–1163. doi: 10.1164/ajrccm/138.5.1157. [DOI] [PubMed] [Google Scholar]
  25. Ireland S. J., Straughan D. W., Tyers M. B. Influence of 5-hydroxytryptamine uptake on the apparent 5-hydroxytryptamine antagonist potency of metoclopramide in the rat isolated superior cervical ganglion. Br J Pharmacol. 1987 Jan;90(1):151–160. doi: 10.1111/j.1476-5381.1987.tb16835.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Joyner W. L., Svensjö E., Arfors K. E. Simultaneous measurements of macromolecular leakage and arteriolar blood flow as altered by PGE1 and beta 2-receptor stimulant in the hamster cheek pouch. Microvasc Res. 1979 Nov;18(3):301–310. doi: 10.1016/0026-2862(79)90038-4. [DOI] [PubMed] [Google Scholar]
  27. Martin R. J., Cicutto L. C., Smith H. R., Ballard R. D., Szefler S. J. Airways inflammation in nocturnal asthma. Am Rev Respir Dis. 1991 Feb;143(2):351–357. doi: 10.1164/ajrccm/143.2.351. [DOI] [PubMed] [Google Scholar]
  28. Persson C. G., Ekman M., Erjefält I. Terbutaline preventing permeability effects of histamine in the lung. Acta Pharmacol Toxicol (Copenh) 1978 May;42(5):395–397. doi: 10.1111/j.1600-0773.1978.tb02223.x. [DOI] [PubMed] [Google Scholar]
  29. Persson C. G., Erjefält I., Grega G. J., Svensjö E. The role of beta-receptor agonists in the inhibition of pulmonary edema. Ann N Y Acad Sci. 1982;384:544–557. doi: 10.1111/j.1749-6632.1982.tb21399.x. [DOI] [PubMed] [Google Scholar]
  30. Persson C. G., Erjefält I. Terbutaline and adrenaline inhibit leakage of fluid and protein in guinea-pig lung. Eur J Pharmacol. 1979 Apr 15;55(2):199–201. doi: 10.1016/0014-2999(79)90392-3. [DOI] [PubMed] [Google Scholar]
  31. Persson C. G. Role of plasma exudation in asthmatic airways. Lancet. 1986 Nov 15;2(8516):1126–1129. doi: 10.1016/s0140-6736(86)90533-7. [DOI] [PubMed] [Google Scholar]
  32. Prasad C. M., Adamski S. W., Svensjö E., Grega G. J. Pharmacological modification of the edema produced by combined infusions of prostaglandin E1 and bradykinin in canine forelimbs. J Pharmacol Exp Ther. 1982 Feb;220(2):293–298. [PubMed] [Google Scholar]
  33. Raymond R. M., Jandhyala B. S., Grega G. J. The interrelationship among bradykinin, various vasoactive substances, and macromolecular permeability in the canine forelimb. Microvasc Res. 1980 May;19(3):329–337. doi: 10.1016/0026-2862(80)90052-7. [DOI] [PubMed] [Google Scholar]
  34. Rippe B., Grega G. J. Effects of isoprenaline and cooling on histamine induced changes of capillary permeability in the rat hindquarter vascular bed. Acta Physiol Scand. 1978 Jul;103(3):252–262. doi: 10.1111/j.1748-1716.1978.tb06212.x. [DOI] [PubMed] [Google Scholar]
  35. Rylander R., Haglind P. Exposure of cotton workers in an experimental cardroom with reference to airborne endotoxins. Environ Health Perspect. 1986 Apr;66:83–86. doi: 10.1289/ehp.866683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Ryley H. C., Brogan T. D. Variation in the composition of sputum in chronic chest diseases. Br J Exp Pathol. 1968 Dec;49(6):625–633. [PMC free article] [PubMed] [Google Scholar]
  37. Sanchis J., Dolovich M., Chalmers R., Newhouse M. Quantitation of regional aerosol clearance in the normal human lung. J Appl Physiol. 1972 Dec;33(6):757–762. doi: 10.1152/jappl.1972.33.6.757. [DOI] [PubMed] [Google Scholar]
  38. Seeger W., Stöhr G., Wolf H. R., Neuhof H. Alteration of surfactant function due to protein leakage: special interaction with fibrin monomer. J Appl Physiol (1985) 1985 Feb;58(2):326–338. doi: 10.1152/jappl.1985.58.2.326. [DOI] [PubMed] [Google Scholar]
  39. Spicer B. A., Baker R. C., Hatt P. A., Laycock S. M., Smith H. The effects of drugs on Sephadex-induced eosinophilia and lung hyper-responsiveness in the rat. Br J Pharmacol. 1990 Dec;101(4):821–828. doi: 10.1111/j.1476-5381.1990.tb14164.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Svensjö E., Grega G. J. Evidence for endothelial cell-mediated regulation of macromolecular permeability by postcapillary venules. Fed Proc. 1986 Feb;45(2):89–95. [PubMed] [Google Scholar]
  41. Tepperman B. L., Whittle B. J. Comparison of the effects of neuropeptide Y and noradrenaline on rat gastric mucosal blood flow and integrity. Br J Pharmacol. 1991 Jan;102(1):95–100. doi: 10.1111/j.1476-5381.1991.tb12138.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Thompson A. B., Daughton D., Robbins R. A., Ghafouri M. A., Oehlerking M., Rennard S. I. Intraluminal airway inflammation in chronic bronchitis. Characterization and correlation with clinical parameters. Am Rev Respir Dis. 1989 Dec;140(6):1527–1537. doi: 10.1164/ajrccm/140.6.1527. [DOI] [PubMed] [Google Scholar]
  43. Twentyman O. P., Finnerty J. P., Harris A., Palmer J., Holgate S. T. Protection against allergen-induced asthma by salmeterol. Lancet. 1990 Dec 1;336(8727):1338–1342. doi: 10.1016/0140-6736(90)92894-n. [DOI] [PubMed] [Google Scholar]
  44. Ullman A., Hedner J., Svedmyr N. Inhaled salmeterol and salbutamol in asthmatic patients. An evaluation of asthma symptoms and the possible development of tachyphylaxis. Am Rev Respir Dis. 1990 Sep;142(3):571–575. doi: 10.1164/ajrccm/142.3.571. [DOI] [PubMed] [Google Scholar]
  45. Ullman A., Svedmyr N. Salmeterol, a new long acting inhaled beta 2 adrenoceptor agonist: comparison with salbutamol in adult asthmatic patients. Thorax. 1988 Sep;43(9):674–678. doi: 10.1136/thx.43.9.674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Wanner A. Clinical aspects of mucociliary transport. Am Rev Respir Dis. 1977 Jul;116(1):73–125. doi: 10.1164/arrd.1977.116.1.73. [DOI] [PubMed] [Google Scholar]
  47. Wenzel S. E., Larsen G. L., Johnston K., Voelkel N. F., Westcott J. Y. Elevated levels of leukotriene C4 in bronchoalveolar lavage fluid from atopic asthmatics after endobronchial allergen challenge. Am Rev Respir Dis. 1990 Jul;142(1):112–119. doi: 10.1164/ajrccm/142.1.112. [DOI] [PubMed] [Google Scholar]
  48. Wenzel S. E., Westcott J. Y., Larsen G. L. Bronchoalveolar lavage fluid mediator levels 5 minutes after allergen challenge in atopic subjects with asthma: relationship to the development of late asthmatic responses. J Allergy Clin Immunol. 1991 Feb;87(2):540–548. doi: 10.1016/0091-6749(91)90013-e. [DOI] [PubMed] [Google Scholar]

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