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 importa...

Full description

Saved in:
Bibliographic Details
Published in:Experimental physiology 2022-04, Vol.107 (4), p.359-373
Main Authors: Zhuang, Xiao‐Ling, Zhu, Zhuang‐Li, Huang, Qiu‐Hong, Yan, Fu‐Rong, Zheng, Si‐Yi, Lai, Su‐Mei, Jiao, Hai‐Xia, Lin, Mo‐Jun
Format: Article
Language:English
Subjects:
Animals
Calcium
Calcium antagonists
calcium channel
Calcium channels (voltage-gated)
Calcium influx
Contractility
Endothelial Cells
Endothelins
Endothelium
Hypertension, Pulmonary - chemically induced
Hypoxia
Magnesium
Magnesium - pharmacology
Mice
Microvasculature
Monocrotaline
Monocrotaline - adverse effects
Nitric oxide
pulmonary arterial hypertension
Pulmonary arteries
Pulmonary Artery
Rats
Rats, Sprague-Dawley
Rodents
Vasoconstriction
Vasodilation
Citations: Items that this one cites
Items that cite this one
Online Access:Request full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. 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.
ISSN:0958-0670
1469-445X
DOI:10.1113/EP090029