BK Ca Channel Activation Attenuates the Pathophysiological Progression of Monocrotaline-Induced Pulmonary Arterial Hypertension in Wistar Rats.

Autor: Ferraz AP; Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Seara FAC; Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.; Department of Physiological Sciences, Federal Rural University of Rio de Janeiro, Seropedica, RJ, Brazil., Baptista EF; Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Barenco TS; Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Sottani TBB; Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Souza NSC; Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Domingos AE; Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Barbosa RAQ; Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Takiya CM; Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Couto MT; Campus Rio de Janeiro, Federal Institute of Education, Science and Technology of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Resende GO; Campus Rio de Janeiro, Federal Institute of Education, Science and Technology of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Campos de Carvalho AC; Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Ponte CG; Campus Rio de Janeiro, Federal Institute of Education, Science and Technology of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Nascimento JHM; Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil. jhmn@biof.ufrj.br.
Jazyk: angličtina
Zdroj: Cardiovascular drugs and therapy [Cardiovasc Drugs Ther] 2021 Aug; Vol. 35 (4), pp. 719-732. Date of Electronic Publication: 2020 Nov 27.
DOI: 10.1007/s10557-020-07115-5
Abstrakt: Purpose: In the present study, the therapeutic efficacy of a selective BK Ca channel opener (compound X) in the treatment of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) was investigated.
Methods: PAH was induced in male Wistar rats by a single injection of MCT. After two weeks, the MCT-treated group was divided into two groups that were either treated with compound X or vehicle. Compound X was administered daily at 28 mg/kg. Electrocardiographic, echocardiographic, and haemodynamic analyses were performed; ex vivo evaluations of pulmonary artery reactivity, right ventricle (RV) and lung histology as well as expression levels of α and β myosin heavy chain, brain natriuretic peptide, and cytokines (TNFα and IL10) in heart tissue were performed.
Results: Pulmonary artery rings of the PAH group showed a lower vasodilatation response to acetylcholine, suggesting endothelial dysfunction. Compound X promoted strong vasodilation in pulmonary artery rings of both control and MCT-induced PAH rats. The untreated hypertensive rats presented remodelling of pulmonary arterioles associated with increased resistance to pulmonary flow; increased systolic pressure, hypertrophy and fibrosis of the RV; prolongation of the QT and T peak -T end intervals (evaluated during electrocardiogram); increased lung and liver weights; and autonomic imbalance with predominance of sympathetic activity. On the other hand, treatment with compound X reduced pulmonary vascular remodelling, pulmonary flow resistance and RV hypertrophy and afterload.
Conclusion: The use of a selective and potent opener to activate the BK Ca channels promoted improvement of haemodynamic parameters and consequent prevention of RV maladaptive remodelling in rats with MCT-induced PAH.
Databáze: MEDLINE
Externí odkaz: