Mg(2+)-induced vasodilation in human forearm vasculature is inhibited by N(G)-monomethyl-L-arginine but not by indometacin.
We have investigated the mechanism of the vasodilator action of Mg(2+) in human forearm resistance vasculature. Venous occlusion plethysmography was used to measure vasodilator responses to Mg(2+) infused via the brachial artery in healthy men, and to determine effects on Mg(2+) responses of indometacin (an inhibitor of cyclo-oxygenase) and of N(G)-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 x min(-1)) increased plasma Mg(2+) concentration to 1.57+/-0.16 mmol x 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 x min(-1) x 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 Mg(2+), whereas L-NMMA inhibited Mg(2+) 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 Mg(2+) in human forearm resistance vasculature.
Dawes
M
M
Department of Clinical Pharmacology, GKT School of Biomedical Sciences, King's College, London, UK. matthew.dawes@kcl.ac.uk
Ritter
J M
JM
D000328:Adult; D001808:Blood Vessels / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D008278:Magnesium Sulfate / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D008278:Magnesium Sulfate; D007213:Indomethacin