Four-day pulse of sodium cromoglycate modulates pulmonary vessel wall remodeling during 21-day hypoxia in rats

ABSTRACT

Aim of the study: Remodeling of pulmonary resistance arteries in rats due to 4-day hypoxia could be successfully suppressed by sodium cromoglycate. In this study, we tested the difference in the suppression between two distinct time patterns of cromoglycate administration during 21-day hypoxia. In the experiment, we focused on some details in both smooth muscle cells and extracellular matrix of pulmonary arterial walls. Methods: During 21-day hypoxia, rats were treated with sodium cromoglycate either in the first four days or in the last four days. The first four days were chosen to test efficiency of an initial pulse of cromoglycate to suppress pulmonary vascular remodeling. The last four-day administration tested possibility to block remodeling post hoc. Results: Initial pulse reduced and modified remodeling in all levels of pulmonary arteries, which comprises neomuscularization of prealveolar arteries, asymmetrical hypertrophy of tunica media in muscular pulmonary arteries and hypertrophy of tunica media and tunica adventitia in large conduit arteries. Terminal pulse had only negligible effect. Conclusions: Only the initial cromoglycate therapy led to significant morphological suppression of remodeling. We therefore assume important role of initial remodeling influencing during long time hypoxia experiment.

KEYWORDS:

• extracellular matrix
• hypoxic remodeling
• matrix metalloproteinase 13
• pulmonary arteries

Acknowledgements

This work was supported by grant N° 74108 of the Grant Agency of Charles University and by grant N° 13–01710S of the Czech Science Foundation GAČR.

The authors are obliged to Prof. F. Kolář (Department of Developmental Cardiology, Institute of Physiology CAS in Prague) for kind lending their hypoxic chamber, and to Prof. P. Hořín (Department of Animal Genetics, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences in Brno) for his kind help with statistic methods.

Conflicts of interest

The authors have no conflict of interest to declare.

Ethical statement

Experiments were performed in accordance with the European Community and NIH guidelines for using experimental animals. All procedures were approved by the Animal Protection Expert Commission of the 2nd Faculty of Medicine.

Footnote

Contributions: (I) Conception and design: All authors; (II) Administrative support: L Vajner; (III) Provision of study materials or patients: T Novotný; (IV) Collection and assembly of data: T Novotný, L Vajner; (V) Data analysis and interpretation: T Novotný, L Vajner; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors

Additional information

Funding

Grantová Agentura, Univerzita Karlova(10.13039/100007543, 74108)