The role of vascular endothelium in nitroglycerin-mediated vasodilation

Abstract

Aims: Nitroglycerin (or glyceryl trinitrate, GTN) has been long considered an endothelium-independent vasodilator because GTN vasodilation is intact in the absence of the endothelium and in the presence of endothelial dysfunction. However, in animal and in vitro models, GTN has been shown to stimulate the release of certain endothelium-derived vasodilators such as nitric oxide (NO) and prostacyclin (PGI₂ ). In addition, chronic GTN therapy leads to endothelial dysfunction. In this series of experiments, we explored how GTN might interact with the vascular endothelium in normal humans, without cardiovascular disease or risk factors associated with abnormalities in vascular function.

Methods: We examined the effect of inhibition of NO, PGI₂ , and epoxyeicosatrienoic acids (EETs, a class of endothelium-derived hyperpolarizing factor) on GTN-mediated vasodilation. We measured arterial blood flow responses to brachial artery infusions of GTN in the absence and presence of L-NMMA (n = 13), ketorolac (n = 14) and fluconazole (n = 16), which are inhibitors of endothelium-derived NO, PGI₂ and EETs, respectively, in healthy volunteers.

Results: Our results demonstrate that inhibition of endothelium-dependent vasodilator mechanisms does not alter forearm resistance vessel responses to GTN.

Conclusion: We conclude that GTN-mediated dilation of forearm resistance vessels is largely independent of vascular endothelium.

Keywords: cardiovascular pharmacology; endothelium; nitric oxide; pharmacokinetic-pharmacodynamic.

Figure 1

Summary of experimental procedures: the procedure timeline for all four experimental conditions GTN = glyceryl trinitrate (or nitroglycerin).

Figure 2

The effect of endothelium inhibition on GTN‐mediated vasodilation: forearm blood flow responses to intra‐arterial infusions of GTN in the absence and presence of endothelium inhibitor L‐NMMA, ketorolac, and fluconazole FBF = forearm blood flow; GTN = glyceryl trinitrate (or nitroglycerin)