Ascorbic acid-induced modulation of venous tone in humans.
Ascorbic acid appears to have vasodilatory properties, but the underlying mechanisms are not well understood. The aims of this study were to define the acute effects of locally infused ascorbic acid in human veins and to explore underlying mechanisms by using pharmacological tools in vivo. Ascorbic acid was infused in dorsal hand veins submaximally preconstricted with the alpha(1)-adrenoceptor agonist phenylephrine or with prostaglandin F(2alpha) in 23 healthy male nonsmokers, and the venodilator response was measured. Ascorbic acid produced dose-dependent dilation with maximum reversal of constriction of 38+/-4% in phenylephrine-preconstricted veins and of 51+/-13% in prostaglandin F(2alpha)-preconstricted veins. Oral pretreatment with the cyclooxygenase inhibitor acetylsalicylic acid or local coinfusion of ascorbic acid and the nitric oxide synthase inhibitor N:(G)-monomethyl-L-arginine had no effect, but coinfusion of ascorbic acid and methylene blue (to inhibit cGMP generation) abolished venodilation. Coinfusion of ascorbic acid and the nonselective potassium channel blocker quinidine abolished venodilation, whereas the inhibitor of ATP-dependent potassium channels glibenclamide had no effect. In cultured bovine endothelial cells, ascorbic acid did not affect intracellular calcium concentration but blunted the response to ATP or digitonin exposure. Ascorbic acid, in millimolar concentrations, dilates human hand veins, presumably by activation of vascular smooth muscle potassium channels through cGMP. This activation is independent of eNOS-mediated nitric oxide synthesis and cyclooxygenase products and does not involve ATP-dependent potassium channels.
Grossmann
M
M
Institute of Clinical Pharmacology, Medical Faculty of the University of Technology Dresden (Germany). grossmann@ikp.de
Dobrev
D
D
Himmel
H M
HM
Ravens
U
U
Kirch
W
W
D000328:Adult; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006225:Hand; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010656:Phenylephrine; D015221:Potassium Channels / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014680:Veins / Q000187:drug effects* / Q000502:physiology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D015221:Potassium Channels; D010656:Phenylephrine; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D001205:Ascorbic Acid; D001241:Aspirin; D002118:Calcium; D008751:Methylene Blue