Abstract
New findings:
What is the central question of this study? The aim was to examine and explore the involvement of Mg2+ in mitigating the vasoconstriction in PAs and sPAs in the MCT-PAH rat model. What are the main finding and its importance? 1.Both SOCE- and ROCE-mediated vasoconstriction enhanced in the MCT-PAH model. 2.High magnesium inhibited vasoconstriction due to directly antagonizing Ca2+ and increasing NO release. 3.The inhibition effect of high magnesium was more notable in sPA.
Abstract:
Increased extracellular magnesium concentration ([Mg2+ ]e ) has been evidenced to attenuate the endothelin-1 (ET-1)-induced contractile response via the release of nitric oxide (NO) from the endothelium in proximal pulmonary arteries (PAs) of chronic hypoxic (CH) 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, the store-operated Ca2+ entry (SOCE)-, and receptor-operated Ca2+ entry (ROCE)-mediated contraction was significantly strengthened. However, there was no upregulation of the vasoconstriction mediated by voltage-dependent calcium entry (VDCE). Furthermore, high magnesium greatly inhibited the VDCE-mediated contraction in PAs instead of sPAs, which was opposite to the ROCE-mediated contraction. Moreover, MCT pretreatment partly eliminated the endothelium-dependent vasodilation 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 inhibition effect of high magnesium on vasoconstriction can be achieved partly by its direct role as a Ca2+ antagonist and partly by increasing the NO release in PMVECs. This article is protected by copyright. All rights reserved.
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