Melatonin Ameliorates Depressive-Like Behaviors in Ovariectomized Mice by Improving Tryptophan Metabolism via Inhibition of Gut Microbe Alistipes Inops.

Melatonin (N-acetyl-5-methoxytryptamine) is reported to improve mood disorders in perimenopausal women and gut microbiome composition is altered during menopausal period. The possible role of microbiome in the treatment effect of melatonin on menopausal depression remains unknown. Here, it is shown that melatonin treatment reverses the gut microbiota dysbiosis and depressive-like behaviors in ovariectomy (OVX) operated mice. This effect of melatonin is prevented by antibiotic cocktails (ABX) treatment. Transferring microbiota harvested from adolescent female mice to OVX-operated mice is sufficient to ameliorate depressive-like behaviors. Conversely, microbiota transplantation from OVX-operated mice or melatonin-treated OVX-operated mice to naïve recipient mice exhibits similar phenotypes to donors. The colonization of Alistipes Inops, which is abundant in OVX-operated mice, confers the recipient with depressive-like behaviors. Further investigation indicates that the expansion of Alistipes Inops induced by OVX leads to the degradation of intestinal tryptophan, which destroys systemic tryptophan availability. Melatonin supplementation restores systemic tryptophan metabolic disorders by suppressing the growth of Alistipes Inops, which ameliorates depressive-like behaviors. These results highlight the previously unrecognized role of Alistipes Inops in the modulation of OVX-induced behavioral disorders and suggest that the application of melatonin to inhibit Alistipes Inops may serve as a potential strategy for preventing menopausal depressive symptoms.

Applying Resistant Starch to Improve the Gel and Water Retention of Reduced-Fat Pork Batter.

Emulsified meat products contain high animal fat content, and excessive intake of animal fat is not good for health, so people are paying more and more attention to reduced-fat meat products. This study investigated the impact of varying proportions of pork back-fat and/or resistant starch on the proximate composition, water and fat retention, texture properties, color, and rheology characteristic of pork batter. The results found that replacing pork back-fat with resistant starch and ice water significantly decreased the total lipid and energy contents of cooked pork batter (p < 0.05) while improving emulsion stability, cooking yield, texture, and rheology properties. Additionally, when the pork back-fat replacement ratio was no more than 50%, there was a significant increase in emulsion stability, cooking yield, hardiness, springiness, cohesiveness, chewiness, and L* and G' values (p < 0.05). Furthermore, resistant starch and ice water enhanced myosin head and tail thermal stability and increased G' value at 80 °C. However, the initial relaxation times significantly decreased (p < 0.05) and the peak ratio of P21 significantly increased from 84.62% to 94.03%, suggesting reduced fluidity of water. In conclusion, it is feasible to use resistant starch and ice water as a substitute for pork back-fat in order to produce reduced-fat pork batter with favorable gel and rheology properties.

The HMGB1-RAGE axis in nucleus accumbens facilitates cocaine-induced conditioned place preference via modulating microglial activation.

INTRODUCTION: Repeated exposure to cocaine induces microglial activation. Cocaine exposure also induces a release of high mobility group box-1 (HMGB1) from neurons into the extracellular space in the nucleus accumbens (NAc). HMGB1 is an important late inflammatory mediator of microglial activation. However, whether the secretion of HMGB1 acts on microglia or contributes to cocaine addiction is largely unknown. METHODS: Rats were trained by intraperitoneal cocaine administration and cocaine-induced conditioned place preference (CPP). Expression of HMGB1 was regulated by viral vectors. Activation of microglia was inhibited by minocycline. Interaction of HMGB1 and the receptor for advanced glycation end products (RAGE) was disrupted by peptide. RESULTS: Cocaine injection facilitated HMGB1 signaling, together with the delayed activation of microglia concurrently in the NAc. Furthermore, the inhibition of HMGB1 or microglia activation attenuated cocaine-induced CPP. Box A, a specific antagonist to interrupt the interaction of HMGB1 and RAGE, abolished the expression of cocaine reward memory. Meanwhile, the inhibition of HMGB1-RAGE interaction suppressed cocaine-induced microglial activation, as well as the consolidation of cocaine-induced memory. CONCLUSION: All above results suggest that the neural HMGB1 induces activation of microglia through RAGE, which contributes to the consolidation of cocaine reward memory. These findings offer HMGB1-RAGE axis as a new target for the treatment of drug addiction.

Using ultrasonic-assisted sodium bicarbonate treatment to improve the gel and rheological properties of reduced-salt pork myofibrillar protein.

To study the impact of ultrasonic duration (0, 30, and 60 min) and sodium bicarbonate concentration (0% and 0.2%) on the gel properties of reduced-salt pork myofibrillar protein, the changes in cooking yield, colour, water retention, texture properties, and dynamic rheology were investigated. The findings revealed that added sodium bicarbonate significantly increased (P < 0.05) cooking yield, hardness, springiness, and strength of myofibrillar protein while reducing centrifugal loss. Furthermore, the incorporation of sodium bicarbonate led to a significant decrease in L⁎, a⁎, b⁎, and white values of cooked myofibrillar protein; these effects were further amplified with increasing ultrasonic duration (P < 0.05). Additionally, storage modulus (G') significantly increased for myofibrillar protein treated with ultrasonic-assisted sodium bicarbonate treatment resulting in a more compact gel structure post-cooking. In summary, the results demonstrated that ultrasonic-assisted sodium bicarbonate treatment could enhance the tightness of reduced-salt myofibrillar protein gel structure while improving the water retention and texture properties.

Effects of low-frequency magnetic field on solubility, structural and functional properties of soy 11S globulin.

BACKGROUND: Soy 11S globulin has high thermal stability, limiting its application in the production of low-temperature gel foods. In this study, the low-frequency magnetic field (LF-MF, 5 mT) treatment (time, 30, 60, 90, and 120 min) was used to improve the solubility, conformation, physicochemical properties, surface characteristics, and gel properties of soy 11S globulin. RESULTS: Compared with the native soy 11S globulin, the sulfhydryl content, emulsifying capacity, gel strength, water-holding capacity, and absolute zeta potential values significantly increased (P < 0.05) after LF-MF treatment. The LF-MF treatment induced the unfolding of the protein structure and the fracture of disulfide bonds. The variations in solubility, foaming properties, viscosity, surface hydrophobicity, and rheological properties were closely related to the conformational changes of soy 11S globulin, with the optimum LF-MF modification time being 90 min. CONCLUSION: LF-MF treatment is an effective method to improve various functional properties of native soy 11S globulin, and this study provides a reference for the development of plant-based proteins in the food industry. © 2024 Society of Chemical Industry.

Effects of Potassium Bicarbonate on Gel, Antioxidant and Water Distribution of Reduced-Phosphate Silver Carp Surimi Batter under Cold Storage.

The changes in storage loss, water distribution status, gel characteristics, thiobarbituric acid reactive substances (TBARSs), total volatile basic nitrogen, and total plate count of cooked reduced-phosphate silver carp surimi batter during cold storage at 4 °C were investigated. The storage loss, content of free water, pH, hardness, TBARSs, total volatile basic nitrogen value, and total plate count of all cooked silver carp surimi batters significantly increased (p < 0.05) with an increase in cold storage time. Meanwhile, the content of immobilized water, whiteness, springiness, and cohesiveness significantly decreased (p < 0.05). At the same cold storage time, the sample of cooked reduced-phosphate silver carp surimi batter had lower water mobility, darker color, and better texture characteristics than the cooked silver carp surimi batter without potassium bicarbonate; however, the values of TBARSs, total volatile basic nitrogen, and total plate count were not significantly different (p > 0.05). This meant that there was no difference between potassium bicarbonate and sodium tripolyphosphate in antioxidant and antibacterial activity during the cold storage of silver carp surimi batter. To summarize, the use of potassium bicarbonate instead of sodium tripolyphosphate could produce cooked reduced-phosphate silver carp surimi batter with better water-holding capacity and gel characteristics during cold storage.

Correction: Orexin-A Promotes Cell Migration in Cultured Rat Astrocytes via Ca2+-Dependent PKCα and ERK1/2 Signals.

[This corrects the article DOI: 10.1371/journal.pone.0095259.].

Cell type-specific NRBF2 orchestrates autophagic flux and adult hippocampal neurogenesis in chronic stress-induced depression.

Dysfunctional autophagy and impairment of adult hippocampal neurogenesis (AHN) each contribute to the pathogenesis of major depressive disorder (MDD). However, whether dysfunctional autophagy is linked to aberrant AHN underlying MDD remains unclear. Here we demonstrate that the expression of nuclear receptor binding factor 2 (NRBF2), a component of autophagy-associated PIK3C3/VPS34-containing phosphatidylinositol 3-kinase complex, is attenuated in the dentate gyrus (DG) under chronic stress. NRBF2 deficiency inhibits the activity of the VPS34 complex and impairs autophagic flux in adult neural stem cells (aNSCs). Moreover, loss of NRBF2 disrupts the neurogenesis-related protein network and causes exhaustion of aNSC pool, leading to the depression-like phenotype. Strikingly, overexpressing NRBF2 in aNSCs of the DG is sufficient to rescue impaired AHN and depression-like phenotype of mice. Our findings reveal a significant role of NRBF2-dependent autophagy in preventing chronic stress-induced AHN impairment and suggest the therapeutic potential of targeting NRBF2 in MDD treatment.

Using Potassium Bicarbonate to Improve the Water-Holding Capacity, Gel and Rheology Characteristics of Reduced-Phosphate Silver Carp Batters.

To study the use of partial or total potassium bicarbonate (PBC) to replace sodium tripolyphosphate (STPP) on reduced-phosphate silver carp batters, all the batters were composed of silver carp surimi, pork back fat, ice water, spices, sugar, and sodium chloride. Therein, the sample of T1 contained 4 g/kg STPP; T2 contained 1 g/kg PBC, 3 g/kg STPP; T3 contained 2 g/kg PBC, 2 g/kg STPP; T4 contained 3 g/kg PBC, 1 g/kg STPP; T5 contained 4 g/kg PBC, and they were all produced using a bowl chopper. The changes in pH, whiteness, water- and oil-holding capacity, gel and rheological properties, as well as protein conformation were investigated. The pH, cooking yield, water- and oil-holding capacity, texture properties, and the G' values at 90 °C of the reduced-phosphate silver carp batters with PBC significantly increased (p < 0.05) compared to the sample without PBC. Due to the increasing pH and enhanced ion strength, more ß-sheet and ß-turns structures were formed. Furthermore, by increasing PBC, the pH significantly increased (p < 0.05) and the cooked silver carp batters became darkened. Meanwhile, more CO2 was generated, which destroyed the gel structure, leading the water- and oil-holding capacity, texture properties, and G' values at 90 °C to be increased and then decreased. Overall, using PBC partial as a substitute of STPP enables reduced-phosphate silver carp batter to have better gel characteristics and water-holding capacity by increasing its pH and changing its rheology characteristic and protein conformation.

CD200 in dentate gyrus improves depressive-like behaviors of mice through enhancing hippocampal neurogenesis via alleviation of microglia hyperactivation.

BACKGROUND: Neuroinflammation and microglia play critical roles in the development of depression. Cluster of differentiation 200 (CD200) is an anti-inflammatory glycoprotein that is mainly expressed in neurons, and its receptor CD200R1 is primarily in microglia. Although the CD200-CD200R1 pathway is necessary for microglial activation, its role in the pathophysiology of depression remains unknown. METHODS: The chronic social defeat stress (CSDS) with behavioral tests were performed to investigate the effect of CD200 on the depressive-like behaviors. Viral vectors were used to overexpress or knockdown of CD200. The levels of CD200 and inflammatory cytokines were tested with molecular biological techniques. The status of microglia, the expression of BDNF and neurogenesis were detected with immunofluorescence imaging. RESULTS: We found that the expression of CD200 was decreased in the dentate gyrus (DG) region of mice experienced CSDS. Overexpression of CD200 alleviated the depressive-like behaviors of stressed mice and inhibition of CD200 facilitated the susceptibility to stress. When CD200R1 receptors on microglia were knocked down, CD200 was unable to exert its role in alleviating depressive-like behavior. Microglia in the DG brain region were morphologically activated after exposure to CSDS. In contrast, exogenous administration of CD200 inhibited microglia hyperactivation, alleviated neuroinflammatory response in hippocampus, and increased the expression of BDNF, which in turn ameliorated adult hippocampal neurogenesis impairment in the DG induced by CSDS. CONCLUSIONS: Taken together, these results suggest that CD200-mediated alleviation of microglia hyperactivation contributes to the antidepressant effect of neurogenesis in dentate gyrus in mice.

Malignancy in dermatomyositis: a mono-centric retrospective study of 134 patients in China and a potential predictive model.

Objectives: To describe the demographics and phenotypes of malignancies-associated dermatomyositis (MADM) in east China and pinpoint potential factors indicative of malignancies in patients with dermatomyositis and establish a predictive model. Methods: We retrospectively analyzed clinical data from 134 patients with adult-onset dermatomyositis hospitalized between January 2019 and May 2022 in one comprehensive hospital. Clinical data including disease course, initial symptoms and signs, and demographic information were retrieved from the Electronic Medical Records System. Other parameters including myositis-specific autoantibodies profiles, ferritin, sedimentation, etc. were all referable. Multivariable multinomial logistic regression was employed to simulate a model to predict cancer risks. Receiver operating characteristic curve was adopted to evaluate the potency of the model. Results: 134 patients with adult-onset dermatomyositis were aptly enrolled in this study based on inclusive and exclusive criteria: 12 (8.96%) with malignancies, 57 (42.53%) with aberrant tumor biomarkers but no malignancies, 65 (48.51%) with neither malignancies nor abnormal tumor biomarkers. Senior diagnostic age, higher LDH, higher ferritin, positive anti-TIF1γ and anti-Mi2 rather than anti-NXP2 autoantibodies were positive indicators of malignancies. Additionally, neither initial complaints nor signs were found to be correlated to a tendency towards malignancies. Digestive system, nasopharyngeal, and lung malignancies were mostly documented in east China. One multivariable multinomial logistic regression model was established to predict the phenotypes of dermatomyositis on the basis of potential malignancies and the overall sensitivity and specificity was satisfactory. Conclusion: Positivity of anti-TIF1γ and anti-Mi2 autoantibodies are highly indicative of malignancies while the role of anti-NXP2 autoantibody in MADM in the Chinese population remains unclear. The phenotypes of malignancies can be predicted through the model and the predictive power is sufficient. More attention should be paid to malignancies screening in patients with aberrant tumor biomarkers but no malignancies, particularly digestive system, nasopharyngeal, and lung malignancies in patients with dermatomyositis but without malignancies.

BNIP3L/NIX-mediated mitophagy alleviates passive stress-coping behaviors induced by tumor necrosis factor-α.

Recent studies based on animal models of various neurological disorders have indicated that mitophagy, a selective autophagy that eliminates damaged and superfluous mitochondria through autophagic degradation, may be involved in various neurological diseases. As an important mechanism of cellular stress response, much less is known about the role of mitophagy in stress-related mood disorders. Here, we found that tumor necrosis factor-α (TNF-α), an inflammation cytokine that plays a particular role in stress responses, impaired the mitophagy in the medial prefrontal cortex (mPFC) via triggering degradation of an outer mitochondrial membrane protein, NIP3-like protein X (NIX). The deficits in the NIX-mediated mitophagy by TNF-α led to the accumulation of damaged mitochondria, which triggered synaptic defects and behavioral abnormalities. Genetic ablation of NIX in the excitatory neurons of mPFC caused passive coping behaviors to stress, and overexpression of NIX in the mPFC improved TNF-α-induced synaptic and behavioral abnormalities. Notably, ketamine, a rapid on-set and long-lasting antidepressant, reversed the TNF-α-induced behavioral abnormalities through activation of NIX-mediated mitophagy. Furthermore, the downregulation of NIX level was also observed in the blood of major depressive disorder patients and the mPFC tissue of animal models. Infliximab, a clinically used TNF-α antagonist, alleviated both chronic stress- and inflammation-induced behavioral abnormalities via restoring NIX level. Taken together, these results suggest that NIX-mediated mitophagy links inflammation signaling to passive coping behaviors to stress, which underlies the pathophysiology of stress-related emotional disorders.

Effects of pre-emulsified safflower oil with magnetic field modified soy 11S globulin on the gel, rheological, and sensory properties of reduced-animal fat pork batter.

In this work, the differences in macrostructure and microstructure, rheology, and storage stability of pre-emulsified safflower oil (PSO) prepared by natural and magnetic field modified soy 11S globulin were analysised. It was concluded that the PSO with magnetic field modified soy 11S globulin (MPSO) has better emulsifying activity and physical stability. The changes in gel quality, oxidational sensitivity, rheological, and sensory properties of pork batters with different substitute ratios (0%, 25%, 50%, 75%, and 100%) of pork back-fat by MPSO with magnetic field modified soy 11S globulin were studied. Compared to the sample without MPSO, pork batter with MPSO showed higher emulsion stability, apparent viscosity, L⁎ value, springiness, cohesiveness, and expressible moisture, while lower a⁎ value and cooking loss. Moreover, added MPSO could be more uniformly distributed into the meat matrix with smaller holes. With the increase in the replacement proportion of pork back-fat, the hardness, water- and fat-holding capacity, and P21 of pork batter significantly decreased (P < 0.05). As revealed by sensory evaluation and TBARS, using MPSO to substitute for pork back-fat decreased the lipid oxidational sensitivity of pork batter, and without negative effects on the appearance, juiciness and overall acceptability. Overall, it is feasible to apply MPSO as a pork-fat replacer to produce reduced-animal fat pork batter with excellent gel and sensory properties.

Microglia-dependent excessive synaptic pruning leads to cortical underconnectivity and behavioral abnormality following chronic social defeat stress in mice.

Synapse loss in medial prefrontal cortex (mPFC) has been implicated in stress-related mood disorders, such as depression. However, the exact effect of synapse elimination in the depression and how it is triggered are largely unknown. Through repeated longitudinal imaging of mPFC in the living brain, we found both presynaptic and postsynaptic components were declined, together with the impairment of synapse remodeling and cross-synaptic signal transmission in the mPFC during chronic stress. Meanwhile, chronic stress also induced excessive microglia phagocytosis, leading to engulfment of excitatory synapses. Further investigation revealed that the elevated complement C3 during the stress acted as the tag of synapses to be eliminated by microglia. Besides, chronic stress induced a reduction of the connectivity between the mPFC and neighbor regions. C3 knockout mice displayed significant reduction of synaptic pruning and alleviation of disrupted functional connectivity in mPFC, resulting in more resilience to chronic stress. These results indicate that complement-mediated excessive microglia phagocytosis in adulthood induces synaptic dysfunction and cortical hypo-connectivity, leading to stress-related behavioral abnormality.

Changes in Gel Characteristics, Rheological Properties, and Water Migration of PSE Meat Myofibrillar Proteins with Different Amounts of Sodium Bicarbonate.

The changes in the gel and rheological properties and water-holding capacity of PSE meat myofibrillar proteins with different amounts of sodium bicarbonate (SC, 0−0.6/100 g) were studied. Compared to the PSE meat myofibrillar proteins with 0/100 g SC, the texture properties and cooking yield significantly increased (p < 0.05) with increasing SC; meanwhile, adding SC caused the gel color to darken. All samples had similar curves with three phases, and the storage modulus (G') values significantly increased with the increasing SC. The thermal stability of the PSE meat myofibrillar proteins was enhanced, and the G' value at 80 °C increased with the increasing SC. Because water was bound more tightly to the protein matrix, the initial relaxation times of T21 and T22 shortened, the peak ratio of P21 significantly increased (p < 0.05), and the P22 significantly decreased (p < 0.05), which implied that the mobility of the water was reduced. Overall, SC could improve the thermal stability of the PSE meat myofibrillar proteins and increase the water-holding capacity and textural properties of the cooked PSE meat myofibrillar protein gels.

Effect of Ultrasound-Assisted Sodium Bicarbonate Treatment on Aggregation and Conformation of Reduced-Salt Pork Myofibrillar Protein.

To study the effects of an ultrasound (0, 30, and 60 min) and sodium bicarbonate (0% and 0.2%) combination on the reduced-salt pork myofibrillar protein, the changes in pH, turbidity, aggregation, and conformation were investigated. After the ultrasound-assisted sodium bicarbonate treatment, the pH increased by 0.80 units, the absolute value of Zeta potential, hydrophobic force, and active sulfhydryl group significantly increased (p < 0.05), and the turbidity and particle size significantly decreased (p < 0.05). Meanwhile, the fluorescence intensity decreased from 894 to 623, and the fluorescence peak showed a significant redshift, which indicated that the ultrasound-assisted sodium bicarbonate treatment exposed the non-polarity of the microenvironment in which the fluorescence emission group was located, leading to the microenvironment and protein structure of myofibrillar tryptophan being changed. Overall, an ultrasound-assisted sodium bicarbonate treatment could significantly improve pork myofibrillar protein solubility and change the protein structure under a reduced-salt environment.

Effect of sodium bicarbonate on techno-functional and rheological properties of pale, soft, and exudative (PSE) meat batters.

In the study, changes in salt-soluble protein (SSP) content, gel properties, rheological characteristic, and microstructure attributes of pale, soft, and exudative (PSE) pork batters with different concentrations of added sodium bicarbonate (0-0.6%) were investigated. The pH, b⁎ value, SSP content, cooking yield, texture properties, emulsion stability, and G' values at 72 °C significantly increased with the increase in sodium bicarbonate, but the texture properties and G' values of the samples with 0.4% and 0.6% did not significantly different, while the a⁎ value significantly decreased. Moreover, a greater G' value at 72 °C was in agreement with a higher hardness value of meat batter. The microstructure of cooked PSE meat batters with 0% and 0.2% sodium bicarbonate had a dense structure, and samples with 0.4% and 0.6% had some large cavities. In conclusion, the use of sodium bicarbonate can enhance the water holding capacity, texture and rheological properties of PSE meat batters by increasing their pH, SSP content, and emulsifying stability.

Effect of ultrasound-assisted sodium bicarbonate treatment on gel characteristics and water migration of reduced-salt pork batters.

To study the potential usefulness of ultrasound (0, 30, and 60 min) and sodium bicarbonate (0 % and 0.2 %) combination on the reduced-salt pork batters, the changes in water holding capacity, gel properties, and microstructure were investigated. The pH, salt-soluble proteins solubility, cooking yield, and b* values of reduced-salt pork batters significantly increased (P < 0.05) with the increase in ultrasound time and the addition of sodium bicarbonate, leading to the hardness, springiness, cohesiveness, and chewiness significantly increased (P < 0.05). Furthermore, the use of ultrasound-assisted sodium bicarbonate treatment caused the reduced-salt pork batters to form a typical spongy structure with more evenly cavities. Due to the initial relaxation time of T21 and T22 were shorter, and the peak ratio of P21 was increased and P22 was decreased after ultrasound-assisted sodium bicarbonate treatment, implying that the mobility of water was reduced. Thus, the use of ultrasound-assisted sodium bicarbonate treatment enabled reduced-salt pork batters to have better gel characteristics and higher cooking yield.

Combined effects of high-pressure processing and pre-emulsified sesame oil incorporation on physical, chemical, and functional properties of reduced-fat pork batters.

In this study, the changes in emulsion stability, colour, textural properties, and protein secondary structure of reduced-fat pork batters (50% pork back-fat and 50% pre-emulsified sesame oil) treated under different pressures (0.1, 200 and 400 MPa) were investigated. The emulsion stability, cooking yield, L* value, texture properties, initial relaxation times of T2b, T21, and T22, and peak ratios of P21 in the samples treated under 200 and 400 MPa significantly increased (p < 0.05) compared with those at 0.1 MPa, but the a* and b* values, and the peak ratio of P22 significantly decreased (p < 0.05). The sample treated at 200 MPa exhibited the best emulsion stability, textural properties, water-holding capacity and sensory scores among the samples. High-pressure processing induced structural changes from α-helical to ß-sheet, ß-turn, and random coil structures, enhancing protein-water incorporation and lowering water mobility. High-pressure processing and pre-emulsified sesame oil improved the techno-functional properties and emulsion stability of reduced-fat pork batters.

High magnesium mitigates the vasoconstriction mediated by different types of calcium influx from monocrotaline-induced pulmonary hypertensive rats.

NEW FINDINGS: What is the central question of this study? What is the involvement of Mg2+ in mitigating the vasoconstriction in pulmonary arteries and smaller pulmonary arteries in the monocrotaline-induced pulmonary arterial hypertension (MCT-PAH) rat model? What are the main finding and its importance? Both store-operated Ca2+ entry- and receptor-operated Ca2+ entry-mediated vasoconstriction were enhanced in the MCT-PAH model. High magnesium inhibited vasoconstriction by directly antagonizing Ca2+ and increasing NO release, and this was more notable in smaller pulmonary arteries. ABSTRACT: Increased extracellular magnesium concentration has been shown to attenuate the endothelin-1-induced contractile response via the release of nitric oxide (NO) from the endothelium in proximal pulmonary arteries (PAs) of chronic hypoxic mice. Here, we further examined the involvement of Mg2+ in the inhibition of vasoconstriction in PAs and distal smaller pulmonary arteries (sPAs) in a monocrotaline-induced pulmonary arterial hypertension (MCT-PAH) rat model. The data showed that in control rats vasoconstriction in sPAs is more intense than that in PAs. In MCT-PAH rats, store-operated Ca2+ entry (SOCE)- and receptor-operated Ca2+ entry (ROCE)-mediated contraction were significantly strengthened. However, there was no upregulation of the vasoconstriction mediated by voltage-dependent calcium entry (VDCE). Furthermore, high magnesium greatly inhibited VDCE-mediated contraction in PAs rather than sPAs, which was the opposite of the ROCE-mediated contraction. Moreover, monocrotaline pretreatment partly eliminated the endothelium-dependent vasodilatation in PAs, which in sPAs, however, was still promoted by magnesium due to the increased NO release in pulmonary microvascular endothelial cells (PMVECs). In conclusion, the findings suggest that both SOCE- and ROCE-mediated vasoconstriction in the MCT-PAH model are enhanced, especially in sPAs. The inhibitory effect of high magnesium on vasoconstriction can be achieved partly by its direct role as a Ca2+ antagonist and partly by increasing NO release in PMVECs.