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

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 Mg 2+ 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 Ca 2+ entry (SOCE)-and receptor-operated Ca 2+ 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 Ca 2+ antagonist and partly by increasing NO release in PMVECs.

Magnesium ions improve vasomotor function in exhausted rats

“…The vascular endothelium plays an important role in regulating vasomotor tone by synthesizing and releasing prostacyclin and NO [ 64 ]. Previous studies have shown that the relaxant action of magnesium was mediated by the endothelial release of NO [ 65 , 66 ]. Moreover, Mg 2+ can inhibit the depolarization effect of Ca 2+ and the excitation-contraction coupling related to Ca 2+ , so Mg 2+ can promote vascular relaxation of blood vessels by inhibiting Ca 2+ channels and their functions [ 67 , 68 ].…”