Comparison of the effects of pentaerythritol tetranitrate and nitroglycerin on endothelium-dependent vasorelaxation in male volunteers

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    There is now evidence that tolerance might not be a class effect, and that the nitrate PETN might be a remarkable exception in this regard. In contrast with other long-acting nitrates, studies with PETN in healthy volunteers showed preserved vasodilatory potency, as well as absence of oxidative stress and endothelial dysfunction [38,55] during continuous treatment with this nitrate. In animals, PETN was reported to prevent endothelial dysfunction as well as atherogenesis [56], which might be mediated by its capacity to induce the antioxidant defense protein heme oxygenase-1 (HO-1).

  • Organic nitrates and nitrate tolerance-state of the art and future developments

    2010, Advances in Pharmacology
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    Nitrates were developed and approved at a time when large-scale, long-term, randomized trials were not required, and the absence of patent rights on these medications does not encourage any industry to finance a large-scale clinical trial. Evidence to date emphasizes the importance of such a trial, as smaller trials have pointed out potential deleterious effects of this therapy: studies in healthy volunteers have demonstrated that nitroglycerin and other nitrates, with the possible exception of PETN, cause endothelial and autonomic dysfunction, and paradoxical coronary vasoconstriction (Caramori et al., 1998; Gori et al., 2002, 2003a; Schulz et al., 2002). In line with these findings, two clinical trials and a metaanalysis showed a trend toward an increase in mortality under nitrate therapy (Table I).

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This research was funded by a Grant-in-Aid B3160 from the Heart and Stroke Foundation of Ontario, Toronto, Ontario, Canada. Drs. Gori and Al-Hesayen are supported by a Research Fellowship, and Dr. Parker is the recipient of a Career Investigator Award from the Heart and Stroke Foundation of Ontario, Toronto, Ontario, Canada.

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