Endothelium-dependent influence of small changes in extracellular magnesium concentration on the tone of feline middle cerebral arteries

The aim of this study was to investigate the effect of small alterations in the extracellular magnesium concentration on the tone of feline middle cerebral arteries and to examine the role of the endothelium in these responses. We measured the isometric tension of isolated arterial rings placed between two stainless steel wires in a tissue chamber containing Krebs-Henseleit solution aerated with a gas mixture containing 95% O₂ and 5% CO₂ at 37°C. After precontraction with noradrenaline, a decrease of the extracellular magnesium concentration from 1.2 mM to 1.0 and 0.8 mM resulted in sustained relaxations, whereas elevation of the extracellular magnesium concentration from 0.8 mM to 1.2 mM caused an increase in vascular tone when the endothelium was intact The magnesium deficiency-related dilations were absent in endothelium-denuded vessels and were inhibited by 5×10⁻⁶ M oxyhemoglobin and 10⁻⁵ M methylene blue, suggesting the involvement of an endothelium-derived relaxing factor in this vascular response. However, 5×l0⁻⁷ M nifedipine or 3×10⁻⁵ M dichlorobenzamil did not affect the magnesium deficiency-related relaxations. Therefore, nifedipine-sensitive calcium channels or the sodium/calcium antiport system are not involved in this vascular action of magnesium. We conclude that small alterations in the extracellular magnesium concentration, possibly within the physiological range, are able to modify the basal formation and release of endothelium-derived relaxing factor and thus alter arterial smooth muscle tone in this vascular bed. This endothelium- and magnesium-dependent system appears to be more sensitive than the direct smooth muscle actions of magnesium and might exert a protective effect against magnesium deficiency-induced direct cerebrovascular contraction.