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

Abstract

Pentaerythritol tetranitrate (PETN) is an organic nitrate that, like nitroglycerin (NTG), undergoes biotransformation to release its active metabolite nitric oxide or a nitric oxide adduct. Importantly, compared with other nitrates, PETN has been shown to have antioxidant properties and to inhibit the progression of atherosclerosis. 1 Hacker A. Muller S. Meyer W. Kojda G. The nitric oxide donor pentaerythritol tetranitrate can preserve endothelial function in established atherosclerosis. Br J Pharmacol. 2001; 132: 1707-1714 Crossref PubMed Scopus (56) Google Scholar , 2 Oberle S. Schwartz P. Abate A. Schroder H. The antioxidant defense protein ferritin is a novel and specific target for pentaerithrityl tetranitrate in endothelial cells. Biochem Biophys Res Commun. 1999; 261: 28-34 Crossref PubMed Scopus (62) Google Scholar Furthermore, animal studies and a recent report from our laboratory suggest that tolerance development does not occur during continuous therapy with PETN. 3 Mullenheim J. Muller S. Laber U. Thamer V. Meyer W. Bassenge E. Fink B. Kojda G. The effect of high-dose pentaerythritol tetranitrate on the development of nitrate tolerance in rabbits (German). Naunyn Schmiedebergs Arch Pharmacol. 2001; 364: 269-275 Crossref PubMed Scopus (18) Google Scholar , 4 Fink B. Bassenge E. Unexpected, tolerance-devoid vasomotor and platelet actions of pentaerythrityl tetranitrate. J Cardiovasc Pharmacol. 1997; 30: 831-836 Crossref PubMed Scopus (55) Google Scholar , 5 Dikalov S. Fink B. Skatchkov M. Bassenge E. Comparison of glyceryl trinitrate-induced with pentaerythrityl tetranitrate-induced in vivo formation of superoxide radicals effect of vitamin C. Free Radic Biol Med. 1999; 27: 170-176 Crossref PubMed Scopus (60) Google Scholar , 6 Jurt U. Gori T. Ravandi A. Babaei S. Zeman P. Parker J.D. Differential effects of pentaerythritol tetranitrate and nitroglycerin on the development of tolerance and evidence of lipid peroxidation a human in vivo study. J Am Coll Cardiol. 2001; 38: 854-859 Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar These effects are consistent with the finding that PETN therapy is not associated with increased plasma concentrations of markers of oxidative stress. 6 Jurt U. Gori T. Ravandi A. Babaei S. Zeman P. Parker J.D. Differential effects of pentaerythritol tetranitrate and nitroglycerin on the development of tolerance and evidence of lipid peroxidation a human in vivo study. J Am Coll Cardiol. 2001; 38: 854-859 Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar In the present report, we investigated the effects of continuous therapy with transdermal NTG compared with oral PETN on endothelium-mediated vasodilation.