Skip to main content
NCBI home page
Thorax logoLink to Thorax
. 1981 Oct;36(10):726–730. doi: 10.1136/thx.36.10.726

A calcium antagonist, nifedipine, modifies exercise-induced asthma.

P J Barnes, N M Wilson, M J Brown
PMCID: PMC471744  PMID: 7036400

Abstract

In eight extrinsic asthmatic subjects (age range 16-38 years) there was a significant reduction (p less than 0.01) in the severity of bronchoconstriction after a treadmill exercise test performed 30 minutes after nifedipine 20 mg sublingually. The maximum fall in peak expiratory flow after exercise was 36.0 +/- SEM 5.3% compared with a maximum fall of 56.5 +/- 4.1% after matched placebo capsules when given in double-blind randomised manner on separate days. There was no significant resting bronchodilation or change in blood pressure or heart rate after nifedipine. there was a significant rise in venous plasma histamine during exercise with placebo (6.1 +/- 0.8 to 13.5 +/- 3.5 nmol/l, p less than 0.01) but no significant increase with nifedipine (4.6 +/- 0.6 to 4.7 +/- 0.6 nmol/l) suggesting that nifedipine inhibits the release of mast cell mediators. The dose of inhaled histamine which provoked a 20% fall in peak expiratory flow was also significantly higher (p less than 0.05) with nifedipine (1.5 +/- 0.31 mg/ml) compared with placebo (2.7 +/- 0.63 mg/ml), indicating that there is a small inhibitory effect on bronchial smooth muscle contractility. Nifedipine is a potent antagonist of calcium ion influx in smooth muscle and secretory cells, and these studies suggest that it may inhibit release of mast cell mediators and reduce bronchial smooth muscle contractility in asthma.

Full text

PDF
726

Selected References

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

  1. Barnes P. J., Brown M. J. Venous plasma histamine in exercise- and hyperventilation-induced asthma in man. Clin Sci (Lond) 1981 Aug;61(2):159–162. doi: 10.1042/cs0610159. [DOI] [PubMed] [Google Scholar]
  2. Barrett-Bee K. J. Ionophore- and antigen-induced histamine release from mast cells and a comparison of their inhibition [proceedings]. Biochem Soc Trans. 1977;5(4):965–967. doi: 10.1042/bst0050965. [DOI] [PubMed] [Google Scholar]
  3. Brown M. J., Ind P. W., Barnes P. J., Jenner D. A., Dollery C. T. A sensitive and specific radiometric method for the measurement of plasma histamine in normal individuals. Anal Biochem. 1980 Nov 15;109(1):142–146. doi: 10.1016/0003-2697(80)90022-6. [DOI] [PubMed] [Google Scholar]
  4. Cerrina J., Denjean A., Alexandre G., Lockhart A., Duroux P. Inhibition of exercise-induced asthma by a calcium antagonist, nifedipine. Am Rev Respir Dis. 1981 Feb;123(2):156–160. doi: 10.1164/arrd.1981.123.2.156. [DOI] [PubMed] [Google Scholar]
  5. Chai H., Farr R. S., Froehlich L. A., Mathison D. A., McLean J. A., Rosenthal R. R., Sheffer A. L., Spector S. L., Townley R. G. Standardization of bronchial inhalation challenge procedures. J Allergy Clin Immunol. 1975 Oct;56(4):323–327. doi: 10.1016/0091-6749(75)90107-4. [DOI] [PubMed] [Google Scholar]
  6. Coburn R. F. The airway smooth muscle cell. Fed Proc. 1977 Dec;36(13):2692–2697. [PubMed] [Google Scholar]
  7. Cox J. S. Disodium cromoglycate (FPL 670) ('Intal'): a specific inhibitor of reaginic antibody-antigen mechanisms. Nature. 1967 Dec 30;216(5122):1328–1329. doi: 10.1038/2161328a0. [DOI] [PubMed] [Google Scholar]
  8. Davies S. E. Effect of disodium cromoglycate on exercise-induced asthma. Br Med J. 1968 Sep 7;3(5618):593–594. doi: 10.1136/bmj.3.5618.593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ekelund L. G., Orö L. Antianginal efficiency of nifedipine with and without a beta-blocker, studied with exercise test. A double-blind, randomized subacute study. Clin Cardiol. 1979 Jun;2(3):203–211. doi: 10.1002/clc.4960020306. [DOI] [PubMed] [Google Scholar]
  10. Farley J. M., Miles P. R. Role of depolarization in acetylcholine-induced contractions of dog trachealis muscle. J Pharmacol Exp Ther. 1977 Apr;201(1):199–205. [PubMed] [Google Scholar]
  11. Fewtrell C. M., Gomperts B. D. Quercetin: a novel inhibitor of Ca2+ influx and exocytosis in rat peritoneal mast cells. Biochim Biophys Acta. 1977 Aug 15;469(1):52–60. doi: 10.1016/0005-2736(77)90325-x. [DOI] [PubMed] [Google Scholar]
  12. Fleckenstein A., Fleckenstein-Grün G., Byon Y. K., Haastert H. P., Späh F. Vergleichende Untersuchungen über die Ca++-antagonistischen Grundwirkungen von Niludipin (Bay a 7168) und Nifedipin (Bay a 1040) auf Myokard, Myometrium und glatte Gefässmuskulatur. Arzneimittelforschung. 1979;29(2):230–246. [PubMed] [Google Scholar]
  13. Foreman J. C., Mongar J. L. Effect of calcium on dextran-induced histamine release from isolated mast cells. Br J Pharmacol. 1972 Dec;46(4):767–769. doi: 10.1111/j.1476-5381.1972.tb06902.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Foreman J. C., Mongar J. L. The action of lanthanum and manganese on anaphylactic histamine secretion. Br J Pharmacol. 1973 Jul;48(3):527–537. doi: 10.1111/j.1476-5381.1973.tb08359.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Forman A., Andersson K. E., Henriksson L., Rud T., Ulmsten U. Effects of nifedipine on the smooth muscle of the human urinary tract in vitro and in vivo. Acta Pharmacol Toxicol (Copenh) 1978 Aug;43(2):111–118. doi: 10.1111/j.1600-0773.1978.tb02244.x. [DOI] [PubMed] [Google Scholar]
  16. Himori N., Taira N. Differential effects of the calcium-antagonistic vasodilators, nifedipine and verapamil, on the tracheal musculature and vasculature of the dog. Br J Pharmacol. 1980 Apr;68(4):595–597. doi: 10.1111/j.1476-5381.1980.tb10848.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jaiprakash S. S., Sahay J. N., Chatterjee S. S., MacDonald G. Efficacy of nifedipine in the treatment of angina pectoris and chronic airways obstruction. Postgrad Med J. 1980 Sep;56(659):624–628. doi: 10.1136/pgmj.56.659.624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lichtenstein L. M. The mechanism of basophil histamine release induced by antigen and by the calcium ionophore A23187. J Immunol. 1975 Jun;114(6):1692–1699. [PubMed] [Google Scholar]
  19. Lynch P., Dargie H., Krikler S., Krikler D. Objective assessment of antianginal treatment: a double-blind comparison of propranolol, nifedipine, and their combination. Br Med J. 1980 Jul 19;281(6234):184–187. doi: 10.1136/bmj.281.6234.184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. McNeill R. S., Ingram C. G. Effect of propranolol on ventilatory function. Am J Cardiol. 1966 Sep;18(3):473–475. doi: 10.1016/0002-9149(66)90072-5. [DOI] [PubMed] [Google Scholar]
  21. Middleton E., Jr Antiasthmatic drug therapy and calcium ions: review of pathogenesis and role of calcium. J Pharm Sci. 1980 Feb;69(2):243–251. doi: 10.1002/jps.2600690244. [DOI] [PubMed] [Google Scholar]
  22. Moskowitz R. M., Piccini P. A., Nacarelli G. V., Zelis R. Nifedipine therapy for stable angina pectoris: preliminary results of effects on angina frequency and treadmill exercise response. Am J Cardiol. 1979 Oct 22;44(5):811–816. doi: 10.1016/0002-9149(79)90202-9. [DOI] [PubMed] [Google Scholar]
  23. Patel K. R. Calcium antagonists in exercise-induced asthma. Br Med J (Clin Res Ed) 1981 Mar 21;282(6268):932–933. doi: 10.1136/bmj.282.6268.932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sinclair D. J. Comparison of effects of propranolol and metoprolol on airways obstruction in chronic bronchitis. Br Med J. 1979 Jan 20;1(6157):168–168. doi: 10.1136/bmj.1.6157.168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ulmsten U., Andersson K. E., Forman A. Relaxing effects of Nifedipine on the nonpregnant human uterus in vitro and in vivo. Obstet Gynecol. 1978 Oct;52(4):436–441. [PubMed] [Google Scholar]
  26. Williams D. O., Barnes P. J., Vickers H. P., Rudolf M. Effect of nifedipine on bronchomotor tone and histamine reactivity in asthma. Br Med J (Clin Res Ed) 1981 Aug 1;283(6287):348–348. doi: 10.1136/bmj.283.6287.348. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES