Kangbin Zhou1, John D Parker1,2,3. 1. Department Pharmacology and Toxicology, the University of Toronto. 2. Division of Cardiology, Department of Medicine, Sinai Health System and the Peter Munk Cardiac Centre, University Health Network, Toronto. 3. The Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto.
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.
RCT Entities:
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.
Authors: Rachel R Markwald; Brett S Kirby; Anne R Crecelius; Rick E Carlson; Wyatt F Voyles; Frank A Dinenno Journal: J Physiol Date: 2011-02-21 Impact factor: 5.182
Authors: Mao Mao; Varadarajan Sudhahar; Kristine Ansenberger-Fricano; Denise C Fernandes; Leonardo Y Tanaka; Tohru Fukai; Francisco R M Laurindo; Ronald P Mason; Jeannette Vasquez-Vivar; Richard D Minshall; Krisztian Stadler; Marcelo G Bonini Journal: Free Radic Biol Med Date: 2011-10-07 Impact factor: 7.376
Authors: Stephen Ph Alexander; Doriano Fabbro; Eamonn Kelly; Neil V Marrion; John A Peters; Elena Faccenda; Simon D Harding; Adam J Pawson; Joanna L Sharman; Christopher Southan; Jamie A Davies Journal: Br J Pharmacol Date: 2017-12 Impact factor: 8.739
Authors: Isla S Mackenzie; Kaisa M Maki-Petaja; Carmel M McEniery; Yi Ping Bao; Sharon M Wallace; Joseph Cheriyan; Sue Monteith; Morris J Brown; Ian B Wilkinson Journal: Arterioscler Thromb Vasc Biol Date: 2005-07-28 Impact factor: 8.311
Authors: S Weber; E Rey; C Pipeau; G Lutfalla; M O Richard; H Daoud-El-Assaf; G Olive; M Degeorges Journal: J Cardiovasc Pharmacol Date: 1983 Sep-Oct Impact factor: 3.105
Authors: Michael D Seddon; Philip J Chowienczyk; Sally E Brett; Barbara Casadei; Ajay M Shah Journal: Circulation Date: 2008-04-07 Impact factor: 29.690