DIETARY-SUPPLEMENT WITH VITAMIN-C PREVENTS NITRATE TOLERANCE

Enhanced formation of superoxide radicals has been proposed to play a major role in the development of nitrate tolerance in humans. We teste d the effects of vitamin C (Vit-C) supplementation on glyceroltrinitra te (GTN)-induced hemodynamic effects during 3-d nonintermittent transd ermal administration of GTN (0.4 mg/h) in nine healthy subjects. Toler ance development was monitored by changes in arterial pressure, dicrot ic 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 (alb ratio of dicrotic pulse), but within 2 d o f initiating GTN, the alb ratio progressively decreased and reached ba sal levels. In addition, there was a progressive loss of the orthostat ic 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 alb ratio was augmented by 310% for the dura tion of the test period. Changes in vascular tolerance in GTN-treated subjects were paralleled by upregulation of the activity of isolated p latelets, which was also reversed by Vit-C administration. These findi ngs demonstrate that dietary supplementation with Vit-C eliminates vas cular tolerance and concomitant upregulation of ex vivo-washed platele t activity during long-term nonintermittent administration of GTN in h umans.