Key result
Maprotiline at 10 mg/kg once daily significantly reduced right ventricular systolic pressure (33.59 vs 43.92 mmHg) and attenuated disease progression in a rat model of monocrotaline-induced pulmonary arterial hypertension.
Why the study?
Does maprotiline improve hemodynamics and vascular remodeling in a rat model of monocrotaline-induced pulmonary arterial hypertension?
Does maprotiline improve hemodynamics and vascular remodeling in a rat model of monocrotaline-induced pulmonary arterial hypertension?
Maprotiline, a tetracyclic antidepressant, binds to soluble guanylate cyclase and attenuates pulmonary hypertension and vascular remodeling in a rat model.
Answers are grounded in this paper and cite their sources.
Hypothesis-generating for maprotiline in PAH; leaves open clinical translation pending human trials.
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.
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Tong et al. (2018) studied Pulmonary arterial hypertension (PAH) (n=56). Maprotiline vs. Vehicle (model group) was evaluated on Right ventricular systolic pressure (RVSP) (p=<0.05). Maprotiline at 10 mg/kg once daily significantly reduced right ventricular systolic pressure (33.59 vs 43.92 mmHg) and attenuated disease progression in a rat model of monocrotaline-induced pulmonary arterial hypertension.
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