The effect of supplemental L-arginine on tolerance development during continuous transdermal nitroglycerin therapy.

Abstract

OBJECTIVES This study was designed to assess the effect of oral L-arginine on the development of tolerance during continuous transdermal nitroglycerin (TD-GTN) therapy. BACKGROUND Continuous TD-GTN therapy leads to complete tolerance within 24 to 48 h. The mechanism(s) responsible for nitrate tolerance are unclear, but there is increasing evidence that nitroglycerin (GTN) leads to superoxide anion production. The trigger for this is unknown, but there is evidence that GTN alters nitric oxide synthase (NOS) function and also leads to reduced L-arginine availability at its site of action with NOS. METHODS Fourteen patients with stable angina pectoris and reproducible treadmill walking time (TWT) until the onset of moderate angina were studied in a placebo-controlled, crossover study. Transdermal GTN (0.4 mg/h) was applied daily for two periods of 5 to 10 days with the patch left in place for 24 h each day. Capsules containing L-arginine (700 mg) or placebo were administered four times daily during a period of TD-GTN therapy. Treadmill walking time was determined before and 4 h after study capsules on day 1 before TD-GTN to assess the effect of L-arginine on exercise performance. On the last day, TWT was determined at 0 h (24 h after TD-GTN and 9 h after study capsule) and 4 h after TD-GTN reapplication and study capsule. After a 5 to 10 day washout period, the study was repeated with the opposite study capsule. RESULTS Treadmill walking time until the onset of moderate angina was not influenced by the short-term administration of L-arginine. During continuous TD-GTN, the administration of L-arginine increased TWT 4 h and 24 h after patch application. This was significantly greater than TWT during administration of placebo capsules (p < 0.05). CONCLUSIONS The administration of L-arginine modified or prevented the development of nitrate tolerance during continuous TD-GTN therapy.

2 Figures and Tables

Statistics

050100150'03'05'07'09'11'13'15'17
Citations per Year

272 Citations

Semantic Scholar estimates that this publication has 272 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Parker2002TheEO, title={The effect of supplemental L-arginine on tolerance development during continuous transdermal nitroglycerin therapy.}, author={John Orval Parker and John D Parker and Robert William Caldwell and Bernice Farrell and Wayne H Kaesemeyer}, journal={Journal of the American College of Cardiology}, year={2002}, volume={39 7}, pages={1199-203} }