Chronic therapy with isosorbide-5-mononitrate causes endothelial dysfunction, oxidative stress, and a marked increase in vascular endothelin-1 expression

European Heart Journal
Matthias OelzeThomas Münzel

Abstract

Isosorbide-5-mononitrate (ISMN) is one of the most frequently used compounds in the treatment of coronary artery disease predominantly in the USA. However, ISMN was reported to induce endothelial dysfunction, which was corrected by vitamin C pointing to a crucial role of reactive oxygen species (ROS) in causing this phenomenon. We sought to elucidate the mechanism how ISMN causes endothelial dysfunction and oxidative stress in vascular tissue. Male Wistar rats (n= 69 in total) were treated with ISMN (75 mg/kg/day) or placebo for 7 days. Endothelin (ET) expression was determined by immunohistochemistry in aortic sections. Isosorbide-5-mononitrate infusion caused significant endothelial dysfunction but no tolerance to ISMN itself, whereas ROS formation and nicotinamide adenine dinucleotidephosphate (NADPH) oxidase activity in the aorta, heart, and whole blood were increased. Isosorbide-5-mononitrate up-regulated the expression of NADPH subunits and caused uncoupling of the endothelial nitric oxide synthase (eNOS) likely due to a down-regulation of the tetrahydrobiopterin-synthesizing enzyme GTP-cyclohydrolase-1 and to S-glutathionylation of eNOS. The adverse effects of ISMN were improved in gp91phox knockout mice and normalized b...Continue Reading

References

May 23, 1995·Proceedings of the National Academy of Sciences of the United States of America·T MünzelD G Harrison
Jun 1, 1993·The Journal of Clinical Investigation·Y OharaD G Harrison
Nov 1, 1996·The American Journal of Physiology·J S Beckman, W H Koppenol
Jul 20, 2000·Journal of Molecular and Cellular Cardiology·J KählerT Münzel
Jul 11, 2001·Journal of Cardiovascular Pharmacology·J KählerT Münzel
Oct 5, 2001·Journal of the American College of Cardiology·T GoriJ D Parker
Oct 5, 2001·Journal of the American College of Cardiology·T Münzel
Dec 1, 2001·Free Radical Biology & Medicine·M WeberG Kojda
Oct 11, 2003·Circulation Research·Andrei L KleschyovThomas Münzel
Jan 21, 2004·Free Radical Biology & Medicine·Andreas DaiberThomas Munzel
Sep 11, 2004·Journal of the American College of Cardiology·Senta MüllerGeorg Kojda
Nov 10, 2004·The New England Journal of Medicine·Anne L TaylorUNKNOWN African-American Heart Failure Trial Investigators
Jun 21, 2005·Journal of Cardiovascular Pharmacology·Michihito SekiyaKouki Watanabe
Oct 1, 2005·Circulation Research·Thomas MünzelAlexander Mülsch
Jun 10, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Matthias OelzeThomas Münzel
Jun 10, 2008·Free Radical Biology & Medicine·Philip WenzelAndreas Daiber
Jan 31, 2009·American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions·Tommaso Gori, Andreas Daiber
Dec 4, 2009·Clinical Research in Cardiology : Official Journal of the German Cardiac Society·Boris SchnorbusAscan Warnholtz
Nov 18, 2010·Advances in Pharmacology·Andreas DaiberTommaso Gori
Jan 6, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Swenja SchuhmacherEberhard Schulz
Jan 29, 2011·Journal of Vascular Research·Matthias OelzeAndreas Daiber
May 18, 2011·Circulation·Thomas MünzelTommaso Gori

❮ Previous
Next ❯

Citations

Sep 26, 2012·European Heart Journal·Tienush Rassaf, Malte Kelm
Mar 13, 2014·European Heart Journal·Michel Komajda, Carolyn S P Lam
Jan 25, 2014·European Heart Journal·Carmel M McEnieryIan B Wilkinson
Jun 2, 2015·Expert Opinion on Pharmacotherapy·Cocco GiuseppeIselin Hans-Ulrich
Aug 13, 2014·Archives of Physiology and Biochemistry·Doina Popov
Mar 1, 2016·Netherlands Heart Journal : Monthly Journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation·Á KovácsN Hamdani
Sep 10, 2014·Journal of Atherosclerosis and Thrombosis·Juan ChenJian-Jun Li
Jul 25, 2014·European Journal of Heart Failure·Burkert PieskeUNKNOWN SOCRATES Investigators and Coordinators
Apr 22, 2014·Life Sciences·Jo G R De Mey, Paul M Vanhoutte
Apr 12, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Martina MontiLucia Morbidelli
Jul 1, 2016·Basic Research in Cardiology·Yuliya MikhedAndreas Daiber
Dec 13, 2016·PloS One·Nadine DietrichHans-Peter Hammes
Oct 21, 2016·Journal of Cardiovascular Medicine·Francesco FattirolliSimone Venturini
Mar 5, 2016·Journal of Cardiovascular Pharmacology and Therapeutics·Sofia Moreira-SilvaJoana Pimenta
Dec 18, 2013·Journal of the American Heart Association·Stephen J GreeneJaved Butler
Jan 10, 2019·International Journal of Molecular Sciences·Andreas DaiberHuige Li
Jul 13, 2013·Wiener klinische Wochenschrift·Hana Matejovska KubesovaJan Matejovsky
Oct 28, 2019·Journal of Cardiovascular Pharmacology·Wei Chih LingDharmani Devi Murugan
Feb 15, 2020·Heart·Thomas Joseph Ford, Colin Berry
Apr 3, 2020·Current Topics in Medicinal Chemistry·Marko BanovicSerge D Nikolic
May 14, 2020·The Journal of Clinical Hypertension·Glenn M StewartChul-Ho Kim
Apr 17, 2020·International Journal of Molecular Sciences·Tommaso Gori
Jun 21, 2020·Scientific Reports·Vu Thao-Vi DaoHarald H H W Schmidt
Nov 22, 2019·Frontiers in Physiology·Domenico D'AmarioFilippo Crea
Nov 3, 2017·Medicinal Research Reviews·Catarina OliveiraFernanda Borges
Sep 24, 2019·Chemico-biological Interactions·Alina HanfAndreas Daiber
Aug 5, 2021·European Journal of Pharmacology·Wen DingQi-Zhu Tang
Aug 10, 2021·The EPMA Journal·Adriana Torres CrignaOlga Golubnitschaja

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiology Journals

Discover the latest cardiology research in this collection of the top cardiology journals.

Antianginal Drugs: Mechanisms of Action

Antianginal drugs, including nitrates, beta-blockers, and calcium channel blockers, are used in the treatment of angina pectoris. Here is the latest research on their use and their mechanism of action.