350 rub
Journal Technologies of Living Systems №1 for 2022 г.
Article in number:
A novel model of pulmonary hypertension as a result of unilateral ischemia of carotid bodies
Type of article: scientific article
DOI: https://doi.org/10.18127/j20700997-202201-03
UDC: 616-092.9
Authors:

M.P. Davydova1, M.A. Markov2

1,2 Lomonosov Moscow State University (Moscow, Russia)

Abstract:

An excessive activity of sympathetic nervous system (SNS) is acknowledged one of the reasons of pulmonary hypertension (PH) development or of its maintaining. Carotid bodies activation is a stimulus of an increase of SNS tone. By an acute experiment it has been established, that even unilateral activation of carotid bodies led to a transitory elevation of pulmonary arteries resistance. We proposed, that a long-term ischemia of the carotid bodies, received blood from one of the carotid arteries, can serve as an independent mechanism of PH development.

The goal of the study is to evaluate of a possibility of steady pulmonary hypertension state development by chronic unilateral ischemia of the carotid bodies in rats.

An ischemia state of the carotid bodies was performed by left common carotid artery transection or by left external carotid artery ligation. One month after the operation a significant elevation of systolic blood pressure (SBP) in heart right ventricle was received after left common carotid artery transection – 35.9 mm Hg vs 30.0 mm Hg in control group, first quartiles - 31.7 mm Hg and 24.3 mm Hg, third quartiles – 41.9 mm Hg and 30.7 mm Hg, accordingly (p<0.05). Also a small, but significant increase of the media area and smooth muscle cells layers number of pulmonary arteries of a small diameter was obtained in this experimental group. Bigger morphometric changes were observed in the group with left external carotid artery ligation. Morphometric results indicate that the increase in the media thickness in the experimental groups (on about 7% and 41% accordingly) occurred due to a hypertrophy of smooth muscle cells and a hyperplasia as well. Despite the presence of the morphometric signs of an elevated resistance in the pulmonary arteries, a hypertrophy of heart right ventricle was not found in any operated group, and obtained changes correspond to the development of moderate PH.

In this study a novel model of the pulmonary hypertension was created and a possibility of pulmonary hypertension development, secondary to unilateral ischemia of carotid bodies area, was confirmed.

Pages: 20-27
For citation

Davydova M.P., Markov M.A. A novel model of pulmonary hypertension as a result of unilateral ischemia of carotid bodies. Technologies of Living Systems. 2022. V. 19. № 1. Р. 20-27. DOI: https://doi.org/10.18127/j20700997-202201-03 (In Russian)

References
  1. Fishman A.P. Aminorex to Fen/Phen. An epidemic foretold. Circulation. 1999. V. 99. № 1. P. 156–161.
  2. Zhou L., Zhang J., Jiang X-M., Xie D-J., Wang J-S., Li L., Li B., Wang Z-M., Rothman A., Lawrie A., Chen Sh-L. Pulmonary artery denervation attenuates pulmonary arterial remodeling in dogs with pulmonary arterial hypertension induced by dehydrogenized monocrotaline. JACC Cardiovasc Interv. 2015. V. 8. № 15. P. 2013–2023.
  3. Liu C., Jiang X-M., Zhang J., Li B., Li J., Xie D-J., Hu Z-Y. Pulmonary artery denervation improves pulmonary arterial hypertension induced right ventricular dysfunction by modulating the local renin-angiotensin-aldosterone system. BMC Cardiovasc. Disord. 2016.
    V. 16. № 1. P. 192. DOI 10.1186/s12872-016-0366-4
  4. Na S., Kim O.S., Ryoo S., Kweon T.D., Choi Y.S., Shim H.S., Oh Y.J. Cervical ganglion block attenuates the progression of pulmonary hypertension via nitric oxide and arginase pathways. Hypertension. 2014. V. 63. № 2. P. 309–315.
  5. Chen S-L., Zhang F-F., Xu J., Xie D-J., Zhou L., Nguyen T., Stone G.W. Pulmonary artery denervation to treat pulmonary arterial hypertension: the single-center, prospective, first-in-man PADN-1 study (first-in-man pulmonary artery denervation for treatment of pulmonary artery hypertension). J. Am. Coll. Cardiol. 2013. V. 62. № 12. P. 1092–1100.
  6. Chen S-L., Zhang H., Xie D-J., Zhang J., Zhou L., Rothman A.M., Stone G.W. Hemodynamic, functional, and clinical responses to pulmonary artery denervation in patients with pulmonary arterial hypertension of different causes: phase II results from the Pulmonary Artery Denervation-1 study. Circ. Cardiovasc. Interv. 2015. V. 8. № 11. P. 28–37.
  7. Sugito K., Tatsumi K., Igari H., Kasahara Y., Tani T., Kimura H., Hayashi F., Kuriyama T. Role of carotid body in pressure response of pulmonary circulation in rats. Respir. Physiol. 1998. V. 111. № 3. P. 283–293.
  8. Markov M.A., Davydova M.P., Usachev D.Yu., Lukshin V.A., Balakhonova T.V., Rodnenkov O.V., Martynyuk T.V. Legochnaya gi-pertenziya u bolnykh s gemodinamicheski znachimym ateroskleroticheskim porazheniyem sonnoy arterii: novyye patofiziolo-gicheskiye mekhanizmy zabolevaniya. Sistemnyye gipertenzii. 2020. T. 17. № 2. S. 61–64. (in Russian).
  9. Bonnet S., Rochefort G., Sutendra G., Archer S.L., Haromy A., Webster L., Hashimoto K., Bonnet S.N., Michelakis E.D. The nuclear factor of activated T cells in pulmonary arterial hypertension can be therapeutically targeted. Proc. Natl. Acad. Sci. USA. 2007. V. 104. № 27. P. 11418–11423.
  10. Bullen J.W., Tchernyshyov I., Holewinski R.J., DeVine L., Wu F., Venkatraman V., Kass D.L., Cole R.N., Van Eyk J., Semenza G.L. Protein kinase A-dependent phosphorylation stimulates the transcriptional activity of hypoxia-inducible factor 1. Sci. Signal. 2016.
    V. 9. № 430. P. 45–69.
  11. Bonnet S., Michelakis E.D., Porter Ch.J., Andrade-Navarro M.A., Thebaud B., Bonnet S., Haromy A., Harry G., Moudgil R., McMurtry M.S., Weier E.K., Archer S.L. An abnormal mitochondrial-hypoxia inducible factor-1α-Kv channel pathway disrupts oxygen sensing and triggers pulmonary arterial hypertension in fawn hooded rats: similarities to human pulmonary arterial hypertension. Circulation. 2006. V. 113. № 22. P. 2630–2641.
Date of receipt: 08.05.2021
Approved after review: 20.05.2021
Accepted for publication: 25.12.2021