Abstract 19498: Co-administration of Atorvastatin Prevents Nitroglycerin-induced Endothelial Dysfunction and Nitrate Tolerance in Humans in vivo
Background: Animal studies have demonstrated that administration of 3-hydroxy-3 methylglutaryl coenzyme A reductase inhibitors can protect against nitroglycerin (GTN)-induced endothelial dysfunction and tolerance, likely through a reduction in oxidative stress. We aimed to assess whether concurrent administration of atorvastatin confer similar protection in humans.
Methods and Results: Thirty-six healthy male volunteers were randomized to receive continuous transdermal GTN (0.6 mg/h) and placebo, atorvastatin (80 mg/day) alone, or continuous transdermal GTN (0.6 mg/h) with concurrent atorvastatin (80 mg/day), all for 7 days. On the second visit, forearm blood flow was measured with venous-occlusion strain gauge plethysmography in response to incremental infusions of acetylcholine (ACh; 7.5, 15, and 30 μg/min). ACh infusions were co-infused first with normal saline (NS), and repeated during the co-infusion of vitamin C (vitC, 24 mg/min). Blood pressure responses to sublingual GTN (0.4 mg) were assessed on both visits. ACh responses in the GTN+placebo group were significantly attenuated compared to those in the GTN+atorvastatin group and the atorvastatin alone group (Figure A, *P<0.05). The co-infusion of vitC completely restored ACh responses in the GTN+placebo group (Figure B, P<0.01 compared to NS co-infusion) but caused no change in either the atorvastatin or the GTN+atorvastatin groups. Systolic blood pressure responses to sublingual GTN did not significantly change between visits in subjects receiving GTN+atorvastatin and atorvastatin alone. Importantly the systolic blood pressure responses to sublingual GTN were significantly blunted on the second visit in the GTN+placebo group (P<0.05).
Conclusions: The present findings demonstrate, for the first time in humans, that atorvastatin prevents both GTN-induced endothelial dysfunction and nitrate tolerance, likely by counteracting the GTN-induced increase in oxidative stress.
- © 2010 by American Heart Association, Inc.