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Updated: Nov 28, 2025
The Left Pneumonectomy Combined with Monocrotaline or Sugen as a Model of Pulmonary Hypertension in Rats
Published on: March 8, 2019
BKCa Channel Activation Attenuates the Pathophysiological Progression of Monocrotaline-Induced Pulmonary Arterial
Ana Paula Ferraz1, Fernando A C Seara1,2, Emanuelle F Baptista1
1Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Purpose:
In the present study, the therapeutic efficacy of a selective BKCa 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 Tpeak-Tend 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 BKCa channels promoted improvement of haemodynamic parameters and consequent prevention of RV maladaptive remodelling in rats with MCT-induced PAH.
Insights
Compound X, a selective BKCa channel opener, effectively treated pulmonary arterial hypertension (PAH) in rats. It improved hemodynamics and prevented right ventricle remodeling in monocrotaline-induced PAH.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Pulmonary Medicine
Background:
- Pulmonary arterial hypertension (PAH) is a severe condition characterized by high blood pressure in the pulmonary arteries.
- Monocrotaline (MCT) injection is a common method to induce PAH in animal models for research purposes.
- Endothelial dysfunction and right ventricle (RV) remodeling are key pathological features of PAH.
Purpose of the Study:
- To investigate the therapeutic potential of a selective BKCa channel opener, designated as compound X, for treating MCT-induced PAH.
- To evaluate the effects of compound X on hemodynamic parameters, vascular reactivity, and RV function in a rat model of PAH.
Main Methods:
- PAH was induced in Wistar rats using a single MCT injection.
- MCT-treated rats received daily administration of compound X (28 mg/kg) or vehicle.
- Evaluations included electrocardiography, echocardiography, hemodynamic analysis, ex vivo pulmonary artery reactivity, RV and lung histology, and molecular markers.
Main Results:
- MCT-induced PAH rats exhibited endothelial dysfunction, RV hypertrophy, fibrosis, increased pulmonary vascular resistance, and autonomic imbalance.
- Compound X demonstrated potent vasodilation in pulmonary artery rings.
- Treatment with compound X significantly reduced pulmonary vascular remodeling, RV hypertrophy, and afterload, improving hemodynamic parameters.
Conclusions:
- Selective activation of BKCa channels with compound X offers a promising therapeutic strategy for PAH.
- Compound X effectively improved hemodynamic function and prevented maladaptive RV remodeling in a preclinical model of PAH.
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