Abstract
See related article, pp 978–987 Organic nitrates are efficacious drugs for treatment of angina pectoris attacks, acute coronary syndromes, pulmonary edema, and hypertensive crisis. They work by releasing nitric oxide (NO•) or a NO•-related compound (eg, nitrosothiols). Thereby, they activate soluble guanylyl cyclase/cyclic GMP–dependent pathways and lead to antiaggregation and vasodilation (preferentially venodilation) resulting in venous pooling, preload and afterload reduction, reduced left ventricular filling pressures, and reduced myocardial oxygen demand.1 This pharmacodynamic profile promises benefits also for chronic treatment of cardiovascular disease like stable coronary heart disease or chronic heart failure. However, the use of organic nitrates is limited by the rapid development of nitrate tolerance. It is driven mainly by a loss of NO bioavailability caused by increase in reactive oxygen species (ROS) like superoxide (O2•−) originating from activated nicotine amide dinucleotide phosphate oxidases, a dysfunctional mitochondrial respiratory chain, or uncoupled NO synthases.1 Especially O2•− undergoes an avid reaction with NO• to yield peroxynitrite (ONOO− …
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.