Mechanisms of magnesium‐induced vasodilation in cerebral penetrating arterioles

Abstract

Magnesium is a well-known neuroprotective and vasodilatory agent in experimental subarachnoid hemorrhage (SAH). We investigated the signaling mechanisms and dose-dependency of extracellular magnesium-induced vasodilation in cerebral penetrating arterioles and also its vasodilatory effects in vessels preconstricted with agonists associated with delayed cerebral vasospasm following SAH. Male rat penetrating arterioles were cannulated. Their internal diameters were monitored. To investigate mechanisms of magnesium-induced vasodilation, inhibitors of endothelial function, potassium channels and endothelial impairment were examined. To simulate cerebral vasospasm several spasmogenic agonists were applied. Increased extracellular magnesium concentration produced concentration-dependent vasodilation, which was partially attenuated by non-specific calcium-sensitive potassium channel inhibitor tetraethylammonium, but not by other potassium channnels inhibitors. Neither the nitric oxide synthase inhibitor L-NNA nor endothelial impairment induced by air embolism reduced the dilation. Although the magnesium-induced vasodilation was slightly attenuated by the spasmogen ET-1, neither application of PF2α nor TXA2 analog effect the vasodilation. Magnesium induced a concentration- and smooth muscle cell-dependent dilation in cerebral penetrating arterioles. Calcium-sensitive potassium channels of smooth muscle cells may play a key role in magnesium-induced vasodilation. These results provide a fundamental background for the clinical use of magnesium in SAH.