Maprotiline Prevents Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats

Abstract

Pulmonary arterial hypertension (PAH) is a progressive disease caused by increased pulmonary artery pressure and pulmonary vascular resistance, eventually leading to right heart failure until death. Soluble guanylate cyclase (sGC) has been regarded as an attractive drug target in treating PAH. In this study, we discovered that maprotiline, a tetracyclic antidepressant, bound to the full-length recombinant sGC with a high affinity (KD = 0.307 μM). Further study demonstrated that maprotiline concentration-dependently inhibited the proliferation of hypoxia-induced human pulmonary artery smooth muscle cells. Moreover, in a monocrotaline (MCT) rat model of PAH, maprotiline (ip, 10 mg/kg once daily) reduced pulmonary hypertension, inhibited the development of right ventricular hypertrophy and pathological changes of the pulmonary vascular remodeling. Taken together, our studies showed that maprotiline may contribute to attenuate disease progression of pulmonary hypertension.

Baicalin prevents pulmonary arterial remodeling in vivo via the AKT/ERK/NF‐κB signaling pathways

“…21 In this study, MCT was used to establish a rat PAH model, which is widely regarded as classical research method of PAH, especially in the field of drug and pharmacology. 22 The pathological process of this disease model includes induction of chronic inflammation, which leads to the proliferation and migration of PASMCs, and the transformation of endothelial cells, leading to remodeling of the pulmonary artery and an increase in pulmonary artery pressure. 19,23 After baicalin intervention, medium and high doses of baicalin significantly reduced the mPAP and RVSP in rats.…”

“…PASMC proliferation and pulmonary vascular remodeling are used as a modulator of PAH development and provide the therapeutic target of the disease, and hence novel effective agents and more approaches remain urgently needed for the treatment currently 21 . In this study, MCT was used to establish a rat PAH model, which is widely regarded as classical research method of PAH, especially in the field of drug and pharmacology 22 . The pathological process of this disease model includes induction of chronic inflammation, which leads to the proliferation and migration of PASMCs, and the transformation of endothelial cells, leading to remodeling of the pulmonary artery and an increase in pulmonary artery pressure 19 , 23 .…”

Maprotiline Suppresses Cholesterol Biosynthesis and Hepatocellular Carcinoma Progression Through Direct Targeting of CRABP1

“…Maprotiline has been recognized as an antidepressant for a long time, however, several studies have reported its anti-inflammatory function ( Rafiee et al, 2016 ) and ability to relieve pulmonary hypertension ( Tong et al, 2018 ). In this paper, we pointed out that maprotiline has an anticancer effect on HCC.…”

“…Due to the low toxicity, good tolerance and adaptability of maprotiline, it is an ideal candidate for functional repurposing. Tong et al (2018) reported that maprotiline may help reduce the progression of pulmonary hypertension in rats, which prompted us to redefine the function of maprotiline.…”

Formulation and Characterization of Solid Lipid Nanoparticles Loading RF22-c, a Potent and Selective 5-LO Inhibitor, in a Monocrotaline-Induced Model of Pulmonary Hypertension

“…The rats were sacrificed to perform functional evaluations, and sampling of pulmonary and cardiac tissue was performed for morphometric measurements. Throughout the 21 days of the experimental protocol, no difference in body weight between the groups was recorded, and it was not registered any animal death (Tabata et al, 1997;Tong et al, 2018).…”