We have investigated the mechanism of the vasodilator action of Mg2+ in human forearm resistance vasculature. Venous occlusion plethysmography was used to measure vasodilator responses to Mg2+ infused via the brachial artery in healthy men, and to determine effects on Mg2+ responses of indometacin (an inhibitor of cyclo-oxygenase) and of NG-monomethyl-L-arginine (L-NMMA, an inhibitor of the L-arginine/nitric oxide, L-arg/NO, pathway). Magnesium sulphate infusion (0.05, 0.1, 0.2 mmol·min–1) increased plasma Mg2+ concentration to 1.57 ± 0.16 mmol·l–1 in venous blood from the infused arm at the highest dose. There was a dose-related increase in forearm blood flow in the infused arm to a maximum of 6.37 ± 1.37 ml·min–1·dl forearm–1 at the highest dose corresponding to an increase of 159 ± 25% in blood flow relative to the non-infused arm. There was no tachyphylaxis during a second infusion following a 21-min recovery period. Indometacin had no effect on vasodilator responses to Mg2+, whereas L-NMMA inhibited Mg2+ responses (area under the dose-response curve) by 43 ± 6% (p = 0.0003 by repeated-measures ANOVA). Therefore the L-arg/NO pathway is responsible, in part, for the vasodilator action of Mg2+ in human forearm resistance vasculature.

1.
Rasmussen HS, Larsen OG, Meier K, Larsen J: Hemodynamic effects of intravenously administered magnesium on patients with ischemic heart disease. Clin Cardiol 1988;11:824–828.
2.
Woods KL, Fletcher S, Roffe C, Haider Y: Intravenous magnesium sulphate in suspected acute myocardial infarction: Results of the second Leicester Intravenous Magnesium Intervention Trial (LIMIT 2). Lancet 1992;339:1553–1558.
3.
Ritter JM, Frazer CE, Taylor GW: pH-dependent stimulation by Ca2+ of prostacyclin synthesis in rat aortic rings: Effects of drugs and inorganic ions. Br J Pharmacol 1987;91:439–446.
4.
Briel RC, Lippert TH, Zahradnik HP: Action of magnesium sulfate on platelet prostacyclin interaction and prostacyclin of blood vessels. Am J Obstet Gynecol 1985;153:232.
5.
Nadler JL, Goodson S, Rude RK: Evidence that prostacyclin mediates the vascular action of magnesium in humans. Hypertension 1987;9:379–383.
6.
Laurant P, Berthelot A: Influence of endothelium on Mg2+-induced relaxation in noradrenalin-contracted aorta from DOCA-salt hypertensive rat. Eur J Pharmacol 1994;258:167–172.
7.
Whitney RJ: The measurement of volume changes in human limbs. J Physiol (Lond) 1953;121:1–27.
8.
Hokanson DE, Sumner DS, Strandness DE Jr: An electrically calibrated plethysmograph for direct measurement of limb blood flow. IEEE Trans Biomed Eng 1975;22:25–29.
9.
Wilson JR, Kapoor SC: Contribution of prostaglandins to exercise-induced vasodilation in humans. Am J Physiol 1993;265:H171–H175.
10.
Robinson BF: Assessment of responses to drugs in forearm resistance vessels and hand veins of man: Techniques and problems; in Kuhlmann J, Wingender W (eds): Dose-Response Relationships of Drugs. Munich, Zuckschwerdt, 1990, pp 40–43.
11.
Matthews JNS, Altman DG, Campbell MJ, Royston P: Analysis of serial measurements in medical research. Br Med J 1990;300:230–235.
12.
Polimeni PS, Page E: Magnesium in heart muscle. Circ Res 1973;33:367–373.
13.
Adams JH, Mitchell JR: The effect of agents which modify platelet behaviour and of magnesium ions on thrombus formation in-vivo. Thromb Haemost 1979;42:603–610.
14.
Lucas MJ, Leveno KJ, Cunningham FG: A comparison of magnesium sulphate with phenytoin for the prevention of eclampsia. N Engl J Med 1995;333:201–205.
15.
Shechter M, Hod H, Chouraqui P, Kaplinsky E, Rabinowitz B: Magnesium therapy in acute myocardial infarction when patients are not candidates for thrombolytic therapy. Am J Cardiol 1995;75:321–323.
16.
Anonymous: ISIS-4. A randomized factorial trial assessing early oral captopril, oral mononitrate and intravenous magnesium sulfate in 58,050 patients with suspected acute myocardial infarction. Lancet 1995;345:669–685.
17.
Opie LH: Proof that glucose-insulin-potassium provides metabolic protection of ischaemic myocardium. Lancet 1999;353:768–769.
18.
D’Angelo EKG, Singer HA, Rembold CM: Magnesium relaxes arterial smooth muscle by decreasing intracellular Ca2+ without changing intracellular Mg2+. J Clin Invest 1992;89:1988–1994.
19.
Dawes M, Chowienczyk PJ, Ritter JM: Effects of inhibition of the L-arginine/nitric oxide pathway on vasodilation caused by β-adrenergic agonists in human forearm. Circulation 1997;95:2293–2297.
20.
Benjamin N, Calver A, Collier J, Robinson B, Vallance P, Webb D: Measuring forearm blood flow and interpreting the responses to drugs and mediators. Hypertension 1995;25:918–923.
21.
Taddei S, Virdis A, Ghiadoni L, Magagna A, Salvetti A: Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension. Circulation 1998;97:2222–2229.
22.
John S, Schlaich M, Langenfeld M, Weihprecht H, Schmitz G, Weidinger G, Schmieder RE: Increased bioavailability of nitric oxide after lipid-lowering therapy in hypercholesterolemic patients. Circulation 1998;98:211–216.
23.
Cardillo C, Kilcoyne C, Quyyumi A, Cannon R, Panza J: Decreased vasodilator response to isoproterenol during nitric oxide inhibition in humans. Hypertension 1997;30:918–921.
24.
Panza J, Casino P, Kilcoyne C, Quyyumi A: Role of endothelium-derived nitric oxide in the abnormal endothelium-dependent vascular relaxation of patients with essential hypertension. Circulation 1993;87:1468–1474.
25.
O’Kane K, Webb D, Collier J, Vallance P: Local L-NG-monomethyl-arginine attenuates the vasodilator action of bradykinin in the human forearm. Br J Clin Pharm 1994;38:311–315.
26.
Tschudi M, Richard V, Bühler FR, Lüscher TF: Importance of endothelium-derived nitric oxide in porcine coronary resistance arteries. Am J Physiol 1991;260:H13–H20.
27.
Moncada S, Rees DD, Schulz R, Palmer RMJ: Development and mechanism of a specific supersensitivity to nitrovasodilators after inhibition of vascular nitric oxide synthesis in vivo. Proc Natl Acad Sci USA 1991;88:2166–2170.
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