Magnesium ion (Mg^(2+)) is a vasodilator, but little is known about its mechanism of action on vascular system. In vitro, extracellular magnesium sulfate (MgSO_(4)) produced relaxation in phenylephrine (PE) or high KCI-precontracted isolated rat thoracic aorta with (+E) or without (-E) endothelium in a concentration-dependent manner. The MgSO_(4)-induced relaxations were not affected by removal of the endothelium. Pretreatment of +E or -E aortic rings with nitric oxide synthase (NOS) inhibitors (20 μM L-NNA, 100 μM L-NAME, 1 μM dexamethasone and 400 μM aminoguanidine), cyclooxygenase inhibitor (10 μM indomethacin), guanylate cyclase inhibitors (10 μM ODQ and 30 μM methylene blue) and Ca^(2+) transport blocker (10 μM ryanodine) did not affect the relaxant effects of MgSO+ 10 Ca^(2+) channel blockers (0.3 10 μM nifedipine and 0.5 10 μM verapamil) completely decreased the relaxant effects of MgSO_(4) in +E and -E aortic rings. However, in Ca^(2+)-free medium, MgSO_(4)-induced vasorelaxation was potentiated and this response was inhibited by nifedipine. Protein kinase C (PKC) inhibitors (1.0 10 μM staurosporine, 0.5 10 μM tamoxifen and 0.1 10 μM H7) or PLC inhibitor (100 10 μM NCDC) markedly decreased the relaxant effects of MgSO_(4) in +E and -E aortic rings.
In vivo, infusion of MgSO_(4) elicited significant decreases in arterial blood pressure. After intravenous injection of nifedipine (150 μg/kg) and NCDC (3 mg/kg), infusion of MgSO_(4) inhibited the MgSO_(4)-lowered blood pressure markedly. However, after intravenous injection of saponin (15 mg/kg), L-NNA (3 mg/kg), L-NAME (5 mg/kg), indomethacin (2 mg/kg), methylene blue (15 mg/kg) and aminoguanidine (10 mg/kg) failed to inhibit it.
These results suggest that endothelial NO-cGMP or prostaglandin pathway is not involved in vasorelaxant or hypotensive action of Mg^(2+) and that these effects are due to the inhibitory action of Mg^(2+) on the Ca^(2+) channel or PLC-PKC pathway, and are due to the competitive influx of Mg^(2+) and Ca^(2+) through the Ca^(2+) channel.
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