Pulmonary Arterial Hypertension Attenuates Vasoconstrictor Responses Caused by Activation of Alpha-1-Adrenoreceptors in the Systemic Circulation

A. A. Abramov; Абрамов А. А.; V. L. Lakomkin; Лакомкин В. Л.; E. V. Lukoshkova; Лукошкова Е. В.; A. V. Prosvirnin; Просвирнин А. В.; V. I. Kapelko; Капелько В. И.; V. S. Kuzmin; Кузьмин В. С.

doi:10.31857/S0869813923100023

Pulmonary Arterial Hypertension Attenuates Vasoconstrictor Responses Caused by Activation of Alpha-1-Adrenoreceptors in the Systemic Circulation

作者: Abramov A.¹, Lakomkin V.¹, Lukoshkova E.¹, Prosvirnin A.¹, Kapelko V.¹, Kuzmin V.¹^,2
隶属关系:
1. Chazov National Medical Research Centre of Cardiology of the Ministry of Health of the Russian Federation
2. Moscow State University
期: 卷 109, 编号 10 (2023)
页面: 1498-1514
栏目: ЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИ
URL: https://journals.rcsi.science/0869-8139/article/view/232291
DOI: https://doi.org/10.31857/S0869813923100023
EDN: https://elibrary.ru/XDTYSI
ID: 232291

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Pulmonary arterial hypertension (PAH) accompanied by an arterial pressure increase in the pulmonary circulation, remodeling of pulmonary arteries and a change in its sensitivity to regulatory factors; PAH is accompanied by activation of the sympathetic nervous system and renin-angiotensin-aldosterone system and increased production of atrial natriuretic peptide. The change in the sensitivity of the vessels of the systemic circulation (SC) to regulatory influences in PAH has not been investigated. Vasoconstrictor reactions in SC with monocrotaline (MCT) were studied in the work models of PAH in rats (Wistar, 350 ± 50 g, 4 months). Mean arterial pressure (MAP) was recorded against the background of a double autonomous blockade with the administration of the α1-adrenergic receptor agonist (α1-AR) phenylephrine (PE) to conscious rats at the start of experiment, then 2 and 4 weeks after the induction of PAH with MCT or saline injection for control animals. Registration of MAP under the action of PE was also performed during angiotensin-II (ATII) infusion. The maximal amplitude (A_max) of the change in MAP and the longest half-return time of MAP (T_∆MAP1/2) to the baseline level in rats in response to the Phe injection were estimated. It was found that in response to PE, Amah did not change in rats with PAH, whereas in control animals it significantly increased. In rats with PAH 2 (n = 6) and 4 weeks after the induction of PAH with MCT, T_∆MAP1/2 is significantly less than in control rats. ATII leads to delayed changes in T_∆MAP1/2 in both control rats and rats with PAH. In rats with MAP, the potentiation with angiotensin T_∆MAP1/2 is significantly less than in control rats. Thus, in animals with PAH, the ability of the resistive arteries of the systemic circulation to maintain tone in response to the activation of α1-AR decreases. In addition, PAH suppresses the ability of ATII to stimulate sympathetic responses in the SC. Firstly, in vivo, it has been demonstrated remodeling and changing the functional state of the pulmonary circulation leads to changes in the regulation of vascular tone of the systemic circulation.

关键词

pulmonary arterial hypertension, vasoconstrictor responses, α1-adrenoreceptors, angiotensin II, regulation of arterial tone

参考

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