Magnesium Sulfate Mitigates the Progression of Monocrotaline Pulmonary Hypertension in Rats

Abstract

We investigated whether magnesium sulfate (MgSO4) mitigated pulmonary hypertension progression in rats. Pulmonary hypertension was induced by a single intraperitoneal injection of monocrotaline (60 mg/kg). MgSO4 (100 mg/kg) was intraperitoneally administered daily for 3 weeks, from the seventh day after monocrotaline injection. Adult male rats were randomized into monocrotaline (MCT) or monocrotaline plus MgSO4 (MM) groups (n = 15 per group); control groups were maintained simultaneously. For analysis, surviving rats were euthanized on the 28th day after receiving monocrotaline. The survival rate was higher in the MM group than in the MCT group (100% versus 73.3%, p = 0.043). Levels of pulmonary artery wall thickening, α-smooth muscle actin upregulation, right ventricular systolic pressure increase, and right ventricular hypertrophy were lower in the MM group than in the MCT group (all p < 0.05). Levels of lipid peroxidation, mitochondrial injury, inflammasomes and cytokine upregulation, and apoptosis in the lungs and right ventricle were lower in the MM group than in the MCT group (all p < 0.05). Notably, the mitigation effects of MgSO4 on pulmonary artery wall thickening and right ventricular hypertrophy were counteracted by exogenous calcium chloride. In conclusion, MgSO4 mitigates pulmonary hypertension progression, possibly by antagonizing calcium.

Cannabidiol Ameliorates Monocrotaline-Induced Pulmonary Hypertension in Rats

“…The aim of our study was to examine the potential preventive effect of chronic CBD administration (10 mg/kg/day for three weeks) on changes in pulmonary hemodynamic characteristics, vascular function and morphology, chosen hemostatic and blood morphology parameters and lung endocannabinoid levels induced in an experimental model of PH in rats. We applied the model of MCT-stimulated PH because it shows a selective toxic effect on pulmonary vessels without an effect on systemic vessels and has consistent pathological findings of PAH in humans and it serves as a preclinical model of PAH to test potential therapeutic agents [ 24 , 26 ].…”

“…Three weeks after MCT injection we observed increases in the following, parameters of the pulmonary (but not systemic heart rate (HR) and systolic blood pressure (SBP)) circulation, which are characteristic for PH—(1) RVSP by about 115%, (2) RV hypertrophy expressed as Fulton index (RV/LV and septum ratio) by about 55% and (3) the adjusted weight of the lungs (by about 55%) suggesting lung edema [ 28 ]. The above hemodynamic alternations in MCT-treated rats could result from morphometric and vascular functional changes, such as endothelial dysfunction; vascular remodeling, as evidenced by media hypertrophy (similarly to [ 24 , 28 ]); and/or changes in vascular responsiveness, i.e., excessive PA constriction to thromboxane A 2 analogue (U46619) and phenylephrine and attenuation of vasodilatory effects of Ach and SNP, as has been also demonstrated by Christou et al [ 29 ]. The latter could result (among other potential causes) from the altered expression and function of receptors for the respective agonists in the pulmonary circulation [ 30 ].…”

“…Importantly, routine blood testing revealed more than a twofold increase in leukocyte count. This may indicate an inflammatory process, which has been shown to play an important role in PH pathogenesis [ 24 ]. However, the exact significance of these latter changes requires detailed study.…”

“…On day 0, MCT was administered as a single, subcutaneous injection (60 mg/kg [ 24 ]) in a volume of 3 mL/kg. Age-matched CTR rats received an equal volume of vehicle.…”

“…Thus, the aim of our study was to examine the effects of chronic preventive treatment with CBD in rat experimental pulmonary hypertension (PH). Note that the terms “PAH” and “PH” are reserved for the human and experimental conditions, respectively [ 24 , 25 , 26 , 27 ]. To evaluate the efficacy of CBD in PH, right ventricular systolic pressure (RVSP), relaxant-constrictor responses and remodeling of isolated PAs, as well as parameters of hemostasis and levels of endocannabinoids and/or endocannabinoid-like compounds in rat monocrotaline (MCT)-induced PH were measured.…”