MAGNESIUM MODULATES ENDOTHELIAL DYSFUNCTION PRODUCED BY ELEVATED GLUCOSE INCUBATION

In aorta taken from diabetic rabbits studied ex vivo or from normal rabbits exposed to increased glucose for 6 h in vitro the endothelium-dependent relaxation to acetylcholine (ACh) is impaired. Magnesium ion concentration influences vascular smooth muscle (VSM) contractility, endothelium-dependent relaxing factor (EDRF) release and prostaglandin production. We wished to determine the effects of changes in magnesium ion concentration on the abnormality induced by elevated glucose concentration (44 mM) in the endothelium-dependent responses observed in isolated rabbit aorta. In phenylephrine (PE)-precontracted vessels, with physiologic salt solution (PSS) containing 1.2 mM magnesium, endothelium-dependent relaxation and endothelium-independent contraction to ACh was not affected by incubation in elevated glucose (44 mM), indomethacin (10(-5)M) treatment, or both. In solution containing 0.6 mM magnesium, the endothelium-dependent relaxation to ACh was impaired in elevated glucose. Indomethacin treatment did not affect endothelium-dependent relaxation in the control solution but partially restored the response to ACh in elevated glucose. Under basal conditions and in the presence of nitric oxide (NO) synthase inhibition, ACh induced a contraction. In low magnesium-containing medium, this contraction was potentiated by the presence of endothelial cells in control (5.5 mM) and even more in elevated glucose concentration (44 mM). The endothelium-dependent contractions were abolished by pretreatment with indomethacin. However, in control magnesium conditions (1.2 mM), an endothelium-dependent component to the ACh contraction was observed only in elevated glucose concentration. Responses to sodium nitroprusside (SNP), KCl, and serotonin, and the contraction to ACh (in the absence of endothelium) were not influenced by elevated glucose, indomethacin treatment, or both. The results suggest that magnesium ions influence production (release) of contractile prostaglandins by vascular endothelium and that this effect is exacerbated by elevated glucose concentration.