title: Dietary supplement with vitamin C prevents nitrate tolerance.
abstract: Enhanced formation of superoxide radicals has been proposed to play a major role in the development of nitrate tolerance in humans. We tested the effects of vitamin C (Vit-C) supplementation on glyceroltrinitrate (GTN)-induced hemodynamic effects during 3-d nonintermittent transdermal administration of GTN (0.4 mg/h) in nine healthy subjects. Tolerance development was monitored by changes in arterial pressure, dicrotic digital pulse pressure, and heart rate. Studies with GTN, Vit-C, or GTN/Vit-C were successively carried out at random in three different series in the same subjects. GTN treatment caused an immediate rise in arterial conductivity (a/b ratio of dicrotic pulse), but within 2 d of initiating GTN, the a/b ratio progressively decreased and reached basal levels. In addition, there was a progressive loss of the orthostatic decrease in blood pressure. However, coadministration of Vit-C and GTN fully maintained the GTN-induced changes in the orthostatic blood pressure, and the rise of a/b ratio was augmented by 310% for the duration of the test period. Changes in vascular tolerance in GTN-treated subjects were paralleled by upregulation of the activity of isolated platelets, which was also reversed by Vit-C administration. These findings demonstrate that dietary supplementation with Vit-C eliminates vascular tolerance and concomitant upregulation of ex vivo-washed platelet activity during long-term nonintermittent administration of GTN in humans.
authors.affiliation: Institute of Applied Physiology, University of Freiburg, Hermann-Herder-Str 7, D-79104 Freiburg, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Bassenge
authors.forename: N
authors.initials: N
authors.lastname: Fink
authors.forename: M
authors.initials: M
authors.lastname: Skatchkov
authors.forename: B
authors.initials: B
authors.lastname: Fink
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001205:Ascorbic Acid / Q000008:administration & dosage*; D001792:Blood Platelets / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D006152:Cyclic GMP / Q000096:biosynthesis; D004032:Diet; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
chemical_list: D013481:Superoxides; D005996:Nitroglycerin; D006152:Cyclic GMP; D001205:Ascorbic Acid; D002118:Calcium