Biomaterial Database

BKCa Channel Activation Attenuates the Pathophysiological Progression of Monocrotaline-Induced Pulmonary Arterial Hypertension in Wistar Rats. 2021

Ana Paula Ferraz, and Fernando A C Seara, and Emanuelle F Baptista, and Thais S Barenco, and Thais B B Sottani, and Natalia S C Souza, and Ainá E Domingos, and Raiana A Q Barbosa, and Christina M Takiya, and Marcos T Couto, and Gabriel O Resende, and Antonio C Campos de Carvalho, and Cristiano G Ponte, and Jose Hamilton M Nascimento

Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

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. 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. 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. 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.

UI	MeSH Term	Description	Entries
D011804	Quinolines
D002120	Calcium Channel Agonists	Agents that increase calcium influx into calcium channels of excitable tissues. This causes vasoconstriction in VASCULAR SMOOTH MUSCLE and/or CARDIAC MUSCLE cells as well as stimulation of insulin release from pancreatic islets. Therefore, tissue-selective calcium agonists have the potential to combat cardiac failure and endocrinological disorders. They have been used primarily in experimental studies in cell and tissue culture.	Calcium Channel Activators,Calcium Channel Agonists, Exogenous,Calcium Channel Agonist,Exogenous Calcium Channel Agonists,Activators, Calcium Channel,Agonist, Calcium Channel,Agonists, Calcium Channel,Channel Activators, Calcium,Channel Agonist, Calcium,Channel Agonists, Calcium
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000081029	Pulmonary Arterial Hypertension	A progressive rare pulmonary disease characterized by high blood pressure in the PULMONARY ARTERY.	Arterial Hypertension, Pulmonary,Hypertension, Pulmonary Arterial
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014655	Vascular Resistance	The force that opposes the flow of BLOOD through a vascular bed. It is equal to the difference in BLOOD PRESSURE across the vascular bed divided by the CARDIAC OUTPUT.	Peripheral Resistance,Total Peripheral Resistance,Pulmonary Vascular Resistance,Systemic Vascular Resistance,Peripheral Resistance, Total,Resistance, Peripheral,Resistance, Pulmonary Vascular,Resistance, Systemic Vascular,Resistance, Total Peripheral,Resistance, Vascular,Vascular Resistance, Pulmonary,Vascular Resistance, Systemic
D014661	Vasoconstriction	The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE.	Vasoconstrictions
D014664	Vasodilation	The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.	Vasodilatation,Vasorelaxation,Vascular Endothelium-Dependent Relaxation,Endothelium-Dependent Relaxation, Vascular,Relaxation, Vascular Endothelium-Dependent,Vascular Endothelium Dependent Relaxation
D016278	Ventricular Function, Right	The hemodynamic and electrophysiological action of the right HEART VENTRICLE.	Right Ventricular Function,Function, Right Ventricular,Functions, Right Ventricular,Right Ventricular Functions,Ventricular Functions, Right
D016896	Treatment Outcome	Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.	Rehabilitation Outcome,Treatment Effectiveness,Clinical Effectiveness,Clinical Efficacy,Patient-Relevant Outcome,Treatment Efficacy,Effectiveness, Clinical,Effectiveness, Treatment,Efficacy, Clinical,Efficacy, Treatment,Outcome, Patient-Relevant,Outcome, Rehabilitation,Outcome, Treatment,Outcomes, Patient-Relevant,Patient Relevant Outcome,Patient-Relevant Outcomes